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PubMed1995

[A rare case of coronary artery perforation by a PTCA guide wire complicating with postinfarction cardiac rupture after thrombolytic therapy].

We report a rare case of coronary artery perforation by a guide wire for percutaneous transluminal coronary angioplasty (PTCA) complicating with postinfarction cardiac rupture (oozing type). The patient had acute myocardial infarction on the extensive anterior wall and developed cardiac rupture followed by serious cardiac tamponade during the emergency PTCA several hours after tissue plasminogen activator (t-PA) given intravenously. The meandering left anterior descending artery (LAD) was found injured by a PTCA guide wire apart from a small oozing-type cardiac rupture near the apex. We repaired urgently the perforated LAD as well as the ruptured left ventricle. It is thus suggested that coronary artery perforation by a PTCA guide wire may occur on meandering coronary arteries and develop a serious hemorrhagic complication, particularly after thrombolytic therapy.

Angioplasty, Balloon, Coronary↗

PubMedDate not supplied

Accessing the scientific literature. The reality of virtual scholarship.

The age-honored practice of plowing through the Index Medicus in a good medical library to meander through citations for treasured finds is an anachronism. Today, clinicians have the astonishing capacity to bring to bear existing knowledge almost effortlessly. Virtual scholarship makes available up-to-date medical citations and their abstracts. There can be access around the clock on any topic in the office, at the bedside, or from home. Computerized searches of the medical literature promote directed continuing education and may enhance clinical care of patients.

Databases, Bibliographic↗

PubMed1998

Expansion of the dendritic tree of motoneurons innervating neck muscles of the adult cat after permanent axotomy.

The morphologic characteristics of neck motoneurons with intact axons were compared with those of neck motoneurons that had been permanently axotomized for 11 to 17 weeks. Motoneurons were identified antidromically, intracellularly stained with horseradish peroxidase (HRP) and examined after reconstructions of their entire dendritic tree. Axotomized motoneurons differed qualitatively and quantitatively from motoneurons with intact axons. The distal branches of axotomized motoneurons exhibited two novel features: some gave rise to tangled appendages that exhibited growth cone-like specializations resembling lamellipodia and filopodia; others followed a meandering path and had unusually large diameters. These branches showed a discontinuous pattern of staining that was similar to the appearance of myelinated axons stained intra-axonally with HRP. A quantitative analysis of the dendritic trees of 13 completely reconstructed dendritic trees (five axotomized motoneurons and eight motoneurons with intact axons) showed that total dendritic surface area, total dendritic length, and total number of branches increased 38, 34, and 215%, respectively, after axotomy. These measurements were confirmed by comparing the sizes of a larger number of motoneurons (16 axotomized and 21 intact), calculated on the basis of correlations between dendritic tree size and proximal dendritic diameter. We conclude, therefore, that neck motoneurons, in contrast to other types of motoneurons, expand their dendritic trees after axotomy. It is suggested that this expansion is a consequence of two mechanisms: one involves dendritic growth, possibly leading to new synaptic connections; the other causes a conversion of some dendrites into axons.

Animals↗

PubMed1999

Tyrosine hydroxylase-immunoreactive elements in the human globus pallidus and subthalamic nucleus.

In contrast to the well-established dopaminergic innervation of the neostriatum, the existence of dopaminergic innervation of the subthalamic nucleus and globus pallidus is controversial. In the present study, tyrosine hydroxylase (TH)-immunoreactive elements were observed by light microscopy after antigen retrieval in the subthalamic nucleus and in the internal and external segments of the globus pallidus in postmortem human brain. Small islands of apparent neostriatal tissue with abundant arborization of fine, TH-immunoreactive axons in the vicinity of calbindin-positive small neurons resembling neostriatal medium spiny neurons were present in the external segment of the globus pallidus. Large numbers of medium-large, TH-immunoreactive axons were observed passing above and through the subthalamic nucleus and through both pallidal segments; these are presumed to be axons of passage on their way to the neostriatum. In addition, fine, TH-immunoreactive axons with meandering courses, occasional branches, and irregular outlines, morphologically suggestive of terminal axon arborizations with varicosities, were seen in both pallidal segments, including the ventral pallidum, and the subthalamic nucleus, consistent with a catecholaminergic (probably dopaminergic) innervation of these nuclei. This finding suggests that, in Parkinson's disease and in animal models of this disorder, loss of dopaminergic innervation might contribute to abnormal neuronal activation in these three nuclei.

Adult↗

PubMed1999

Comparing measures of travel distances in primates: methodological considerations and socioecological implications.

Travel costs can influence numerous aspects of the lives of primates, including net energy balance (and therefore reproductive success of females) and maximum group size. Despite their potential impact, there has been no systematic comparison of different measures of travel distance. We compared three measures of travel distance in 30 min (actual distance of individuals, straight-line distance of individuals, and straight-line distance of groups) and their ratios in a small group and a large group of vervet monkeys (Cercopithecus aethiops) and between the large group of vervets and a group of patas monkeys (Erythrocebus patas) of roughly similar size. The large group of vervets traveled farther than the small group regardless of the measure used, but the ratios of the different measures were not significantly different between those groups. Patas monkeys traveled significantly farther than the large group of vervets regardless of the measure used. In both vervets and patas, straight-line distances of individuals (ISLD) and groups (GSLD) underestimated actual distances traveled by individuals (IAD), but the degree to which they did so differed between species. IAD is more accurate than the other two measures and is preferred for studies of energetics and individual reproductive success, although ISLD or GSLD may be substituted when the ratios of IAD/ISLD or IAD/GSLD do not differ between groups or species. The ratio of IAD/ISLD was larger in vervets than in patas, suggesting that individual vervets meander more over short periods of time than patas. The ratio of ISLD/GSLD was larger in patas than in vervets, suggesting that patas move at angles or across the group's center-of-mass whereas vervets move more consistently along with others in their group. This has implications for the formation of spatial subgroups and alliances within groups.

Animals↗

PubMed1983

The Sertoli cell junctional complex: structure and permeability to filipin in the neonatal and adult guinea pig.

The development and maintenance of the Sertoli cell junctional complex were investigated in prepubertal and adult guinea pigs. To correlate the structure of the blood-testis barrier with its permeability, the polyene antibiotic filipin (a cholesterol-binding agent of low molecular weight: 570.70) was added to the fixative as a tracer visible in freeze-fracture replicas. Discontinuous zonules, intermediate junctions (i.e., adhering fasciae) and gap junctions all proved permeable to filipin in the two age groups. Only the continuous occluding zonules characteristic of the adult guinea pig's testis were impermeable to the tracer. In pubertal animals, the establishment of the blood-testis barrier coincided with the completion of the junctional strands in occluding zonules. The formation of occluding zonules was similar in the newborn and the adult. In the adult, the Sertoli cell junctional complexes contained three types of cell junctions: occluding, adhering, and gap junctions. The sequence of occluding and adhering junctions from the base to the apex of the epithelium was the reverse of that demonstrated in most epithelia. The impermeable continuous occluding zonules at the base showed parallel patterns of uninterrupted junctional strands, whereas the permeable discontinuous zonules found higher in the epithelium showed a meandering pattern of broken strands. Our observations indicate that (1) Sertoli cell junctional complexes form near the young germinal cells at the base of the seminiferous epithelium and break down near the older germinal cells toward the apex; (2) the various patterns and orientations of the junctional strands reflect, respectively, the different stages of disintegration of the occluding zonules and the conformation of the mature Sertoli cell to the irregular contours of the germinal cells; (3) there is no relationship between permeability and junctional strand orientation; and (4) the cellular contacts between Sertoli cells and germinal cells situated below the blood-testis barrier may represent the early stages of formation of junctional elements which ultimately become incorporated into the Sertoli cell junctional complex.

Animals↗

PubMed2001

Raman signatures of ligand binding and allosteric conformation change in hexameric insulin.

Hexameric insulin is an allosteric protein that undergoes transitions between three conformational states (T(6), T(3)R(3), and R(6)). These allosteric states are stabilized by the binding of ligands to the phenolic pockets and by the coordination of anions to the His B10 metal sites. Raman difference (RD) spectroscopy is utilized to examine the binding of phenolic ligands and the binding of thiocyanate, p-aminobenzoic acid (PABA), or 4-hydroxy-3-nitrobenzoic acid (4H3N) to the allosteric sites of T(3)R(3) and R(6). The RD spectroscopic studies show changes in the amide I and III bands for the transition of residues B1-B8 from a meandering coil to an alpha helix in the T-R transitions and identify the Raman signatures of the structural differences among the T(6), T(3)R(3), and R(6) states. Evidence of the altered environment caused by the approximately 30 A displacement of phenylalanine (Phe) B1 is clearly seen from changes in the Raman bands of the Phe ring. Raman signatures arising from the coordination of PABA or 4H3N to the histidine (His) B10 Zn(II) sites show these carboxylates give distorted, asymmetric coordination to Zn(II). The RD spectra also reveal the importance of the position and the type of substituents for designing aromatic carboxylates with high affinity for the His B10 metal site.

Allosteric Site↗

PubMed2004

Structure-composition relations for the partly disordered Hume-Rothery phase Ir7+7deltaZn97-11delta (0.31< or =delta< or =0.58).

The crystal structure, its variation within the homogeneity range and some physical properties of the new zinc-rich, partly disordered phase Ir7+7deltaZn97-11delta (0.31< or =delta< or =0.58) are reported. The structures of three phases with distinct composition were determined by means of single crystal X-ray diffraction. Ir7+7deltaZn97-11delta exhibits a significant homogeneity range, adopts a complex gamma-brass related cubic structure (cF403-406), is stable up to 1201(2) K, and transforms sluggishly below 1048(4) K into a phase with 394 atoms in the monoclinic primitive unit cell. It is a diamagnetic, moderate metallic conductor. Six distinguishable clusters consisting of 22-29 atoms comprise the structure. The clusters are situated about the 16 high symmetry points of the cubic F lattice. The structure can be subdivided into two partial structures, one with constant composition IrZn5 and 192 atoms per unit cell and a second being significantly richer in zinc with variable composition and 211-214 atoms per unit cell. The meandering triply periodic minimal surface of two interpenetrating diamond-like nets separates the compositionally variable from its complementary invariant part. The phase width is coupled with substitutional and positional disorder. A comprehensive analysis of composition-dependent site occupancy factors reveals a linear correlation between the various types of disorder which can be conclusively interpreted in terms of an incoherent intergrowth of distinctive partial structures in variable proportions on a length scale comparable to the size of the approximately 2 nm large unit cell. On the basis of the structural findings we derive the structure chemically meaningful formula Ir7+7delta)Zn97-11delta which quantitatively accounts for the interrelation between substitutional and positional disorder and provides a measure for the homogeneity range in structural terms.

Alloys↗

PubMed2003

Removal of polysialic acid induces aberrant pathways, synaptic vesicle distribution, and terminal arborization of retinotectal axons.

Developing chick retinotectal projections extend rostrally in the superficial stratum opticum of the tectum until they reach their appropriate target zone. They then penetrate, arborize, and form synapses within distinct tectal retinorecipient layers. In this study, we show that the polysialylated neural cell adhesion molecule is expressed both on the membrane of these developing projections and in the stratum opticum and retinorecipient layers during the period of optic innervation. On this basis, the role of polysialic acid was analyzed with respect to both trajectory and arborization in the tectum, using confocal imaging of DiI-labeled retinotectal fibers in whole-mount tecta of embryos pretreated with a polysialic acid-specific degrading enzyme, endoneuraminidase N. The removal of polysialic acid caused several distinct abnormalities, including random dorsal/ventral meandering of fibers in the stratum opticum, a distorted branching and extension of arbors in the retinorecipient layers, and inappropriate synaptic vesicle accumulation in pretarget areas. These findings indicate that the unique ability of polysialic acid to regulate different types of cell interactions is an essential component of axon behavior during multiple steps of tectal target innervation.

Animals↗

PubMed2005

Modulation of intercellular calcium signaling by melatonin in avian and mammalian astrocytes is brain region-specific.

Calcium waves among glial cells impact many central nervous system functions, including neural integration and brain metabolism. Here, we characterized the modulatory effects of melatonin, a pineal neurohormone that mediates circadian and seasonal processes, on glial calcium waves derived from different brain regions and species. Diencephalic and telencephalic astrocytes, from both chick and mouse brains, expressed melatonin receptor proteins. Further, using the calcium-sensitive dye Fluo-4, we conducted real-time imaging analyses of calcium waves propagated among mammalian and avian astrocytes. Mouse diencephalic astrocytic calcium waves spread to an area 2-5-fold larger than waves among avian astrocytes and application of 10 nM melatonin caused a 32% increase in the spread of these mammalian calcium waves, similar to the 23% increase observed in chick diencephalic astrocytes. In contrast, melatonin had no effect on calcium waves in either avian or mammalian telencephalic astrocytes. Mouse telencephalic calcium waves radially spread from their initiation site among untreated astrocytes. However, waves meandered among mouse diencephalic astrocytes, taking heterogeneous paths at variable rates of propagation. Brain regional differences in wave propagation were abolished by melatonin, as diencephalic astrocytes acquired more telencephalon-like wave characteristics. Astrocytes cultured from different brain regions, therefore, possess fundamentally disparate mechanisms of calcium wave propagation and responses to melatonin. These results suggest multiple roles for melatonin receptors in the regulation of astroglial function, impacting specific brain regions differentially.

Analysis of Variance↗

PubMed1984

Appearance and distribution of neurofilament immunoreactivity in iris nerves.

We have used antiserum raised against neurofilament (NF) protein and indirect immunofluorescence techniques to visualize neuronal structures in rodent, cat, and cow irides. In the adult rat iris a large population of nerve fibers with a nonautonomic distribution show NF-like immunoreactivity. In whole mounts, smooth fluorescent fibers were seen in a fine-meshed plexus from the sphincter margin to the ciliary processes. Superimposed, a sparse pattern of thick meandering axon bundles were seen. Electroblotting and peroxidase immunochemical staining techniques unequivocally showed the presence of all three NF polypeptides in the adult rat iris. Adult mouse irides showed a somewhat sparser pattern of NF-positive nerves than that of the rat. Adult guinea pig irides contained irregular NF-positives fibers and few axon bundles. In cryostat-sectioned cat iris numerous irregularly distributed individual fibers were found, whereas in similarly sectioned cow iris thick NF-positive axon bundles were more numerous. By embryonic day 18 numerous sparse NF-positive axons were seen, and the subsequent gradual increase in both axons in bundles and fine-meshed plexuses of individual fibers produced an appearance similar to that in the adult by 6 days of postnatal age. One week after grafting of irides to the anterior eye chamber, most NF-positive nerves had disappeared from the iris grafts. Sympathetic and parasympathetic denervation of the irides did not influence the distribution of the NF-positive iris nerves. Five days after electrothermal lesion of the trigeminal nerve just distal to its ganglion a large proportion of the NF-positive nerves had disappeared from the iris. All perikarya in the parasympathetic ciliary and most perikarya in the superior cervical sympathetic and in the trigeminal sensory ganglion showed NF immunoreactivity. The present report shows a way to visualize nonautonomic nerve populations in stretch-prepared as well as sectioned irides by immunofluorescence techniques using an antiserum to neurofilament protein.

Animals↗

PubMed1985

Effects of age on Meissner corpuscles: a study of silver-impregnated neurites in mouse digital pads.

Investigation focused on finding qualitative and quantitative evidence of age-changes in the quantity of neural surface within Meissner corpuscles. These mechanoreceptors were studied in 53 mice (nine age-groups) ranging from 1.7 to 24 months old. Forepaw digital pads were formalin-fixed and frozen-sectioned parallel to each digit and perpendicular to the skin. Serial sections were then silver-impregnated to allow light microscopic examination of the neurites (axons) in corpuscles. From young (1.7-7 months) to middle age (9-15 months), neurites became more coarse, tortuous, ramified, varicose, and thus more complex. At old age (18-24 months), neurites seemed attenuated and showed more of an irregular winding, twisted, or tangled pattern with less parallel orientation to the skin surface than the regular spiraled, looped, or arched pattern typical at young and middle ages. Corpuscle size appeared greatest at middle age, smallest at young age. Dermal papillae not occupied by corpuscular neurites were most abundant at old age. The number of corpuscles per area and neurites per corpuscle decreased significantly with age, whereas the number of neurite bifurcations per corpuscle increased significantly. Morphometric analysis of neurites projected by a camera lucida onto a planimeter showed that the length of neurites meandering through a fixed interval of tissue increased significantly until age 12 months-evidence of increased tortuosity; the area of neurites measured within the same fixed interval, and the area of neurite terminals changed significantly as inverse parabolic functions of age-evidence of increased volume until middle age, which decreased thereafter. The general trend of these changes implied growth at young age and atrophy at old age.(ABSTRACT TRUNCATED AT 250 WORDS)

Aging↗

PubMed1996

Novel acrylamido monomers with higher hydrophilicity and improved hydrolytic stability: III. DNA separations by capillary electrophoresis in poly (N-acryloylaminopropanol).

Separation of DNA fragments in a novel polymer network, consisting of N-acryloylaminopropanol (AAP) is reported. The performance of this novel monomer, as a sieving liquid polymer in capillary zone electrophoresis, was evaluated. In 50 microns ID capillaries, an 8% solution of poly (AAP) can afford apex-resolution of the 123/124 bp adjacent pair of DNA fragments in marker V, typically unresolved in any poly (acrylamide) formulation. It is proposed that the distal-OH group in the AAP molecule can form transient H-bonds with the DNA double helix. Molecular modeling shows a meandering structure for poly (AAP), lacing the walls of half a cylinder, with kinks protruding at regular intervals, potentially able to fit into the major groove of DNA. Contrary to previously held beliefs, there seems to be a minimum length of the polymer for proper sieving of DNAs. For poly (acrylamides), a weight average molecular mass Mw 30 000 polymer offers no resolution, whereas a polymer of 250 000 to 400 000 Da exhibits optimum resolving power. For poly (AAP), the optimal length is in excess of 450 000 Da in Mw. Thus, it is shown that both the chemical composition of the monomer and the length of the polymer play a subtle, cooperative role in DNA separation.

Acrylic Resins↗

PubMed2004

Solution structure of the highly acidic protein HI1450 from Haemophilus influenzae, a putative double-stranded DNA mimic.

The solution structure of the acidic protein HI1450 from Haemophilus influenzae has been determined by NMR spectroscopy. HI1450 has homologues in ten other bacterial species including Escherichia coli, Vibrio cholerae, and Yersinia pestis but there are no functional assignments for any members of the family. Thirty-one of the amino acids in this 107-residue protein are aspartates or glutamates, contributing to an unusually low pI of 3.72. The secondary structure elements are arranged in an alpha-alpha-beta-beta-beta-beta order with the two alpha helices packed against the same side of an anti-parallel four-stranded beta meander. Two large loops, one between beta1 and beta2 and the other between beta2 and beta3 bend almost perpendicularly across the beta-strands in opposite directions on the non-helical side of the beta-sheet to form a conserved hydrophobic cavity. The HI1450 structure has some similarities to the structure of the double-stranded DNA (dsDNA) mimic uracil DNA glycosylase inhibitor (Ugi) including the distribution of surface charges and the position of the hydrophobic cavity. Based on these similarities, as well as having a comparable molecular surface to dsDNA, we propose that HI1450 may function as a dsDNA mimic in order to inhibit or regulate an as yet unidentified dsDNA binding protein.

Amino Acid Sequence↗

PubMed1996

Perturbation of the developing Xenopus retinotectal projection following injections of antibodies against beta1 integrin receptors and N-cadherin.

We have examined the function of beta1 integrin receptors and N-cadherin in the development of the Xenopus retinotectal projection. In vivo perturbation experiments were performed by injecting antibodies directed against beta1 integrin receptors and N-cadherin into the embryonic optic pathway. The antibodies were present during the initial development of the retinal projection, when the axons of the ganglion cells are migrating through the optic tract and terminating within the optic tectum. When injected individually, the antibodies were insufficient to cause obvious pathfinding errors. However, when injected together, the antibodies caused specific abnormalities in the development of the retinotectal projection. Pathfinding errors most commonly observed included ectopically projecting axons within the optic tract region, meandering and splaying of axons in the optic tectum, and the induction of prominent ipsilateral projections. IgGs and Fab' fragments of the antibodies produced pathfinding errors; these defects were not observed in animals injected with control antibodies. These in vivo results show that beta1 integrin receptors and N-cadherin have important roles during the development of the visual projection and provide evidence that a balance between cell-cell and cell-matrix adhesion may be critical for the normal development of the vertebrate visual system.

Animals↗

PubMed2002

Thermotropic behavior of poly(oxyethylene) cholesterol ethers.

The thermotropic behavior of poly(oxyethylene) cholesterol ether surfactants was studied by differential scanning calorimetry and small-angle X-ray scattering. Contrary to what is usually observed in conventional poly(oxyethylene)-type surfactant systems, poly(oxyethylene) cholesterol ether surfactants show a change of the fusion mechanism as the chain length is varied. For long chain lengths (n > or = 15) the usual solid-liquid transition is found, but for short chain lengths (n < or = 10) the transition goes through a birefringent lamellar phase. The appearance of this liquid crystal (LC) phase seems to be related with the predominance of the cholesterol part in the short chain polyoxyethylene surfactants. On the contrary, for long polyexyethylene chains the polymer gains in importance and only a solid crystalline structure is observed at low temperatures. An antiparallel packing structure with totally overlapped chains is found for both, the solid and the LC phase. The chains seem to be in a zigzag configuration, and only for the longest surfactant here studied (n = 30) a change of the chain configuration to a much shorter meander configuration is observed.

Calorimetry, Differential Scanning↗

PubMedDate not supplied

Mammals and rainfall: paleoecology of the middle Miocene at La Venta (Colombia, South America).

A comparison of the species richness and macroniche composition of diet, locomotor and body-size classes among 16 nonvolant mammalian faunas in tropical South America reveals numerous significant positive correlations with rainfall. In particular, significant and strong positive correlations with rainfall are found in 18 attributes, including the number of nonvolant mammal species, number of primate species, number of frugivores, primary consumers, arborealists, and the number of species between 100 g to 10 kg in body weight. Estimates of annual rainfall derived from least-squares and polynomial regressions and principal components analysis yield a modal estimate of between 1500 and 2000 mm annual rainfall for the Monkey Beds assemblage at La Venta. This level of rainfall is associated today with the transition between savanna and forest environments in lowland equatorial South America. Paleontological evidence strongly suggests the presence of forest biotopes at La Venta. Paleontologic and sedimentologic evidence together indicate a dynamic and heterogeneous riparian mosaic associated with the shifting course of meandering rivers. Faunal evidence also suggests that habitat heterogeneity and canopy discontinuity extended into the interfluvial area. Seasonal rainfall was probably only of secondary importance in shaping the structural and spatial configuration of the dominantly forested mosaic habitat at La Venta. The fossil record is not consistent with the presence of extensive primary or undisturbed, continuous-canopy, evergreen tropical rainforest. The reconstructed middle Miocene environment at La Venta differs significantly from modern environments of similar geography on the piedmont east of the Andes at the same latitude. This in turn suggests that the extensive evergreen rainforests of the upper Amazonian piedmont that today receive more than 4000 mm of rainfall may post-date the initiation of Andean uplift.

Animals↗

PubMed1995

The refined X-ray structure of muconate lactonizing enzyme from Pseudomonas putida PRS2000 at 1.85 A resolution.

We report here the refined X-ray crystal structure of muconate lactonizing enzyme (MLE) from Pseudomonas putida PRS2000 at a resolution of 1.85 A with an R-factor of 16.8%. An enzyme from the beta-ketoadipate pathway, MLE catalyses the conversion of cis,cis-muconate to muconolactone. It is a homo-octamer, one monomer consisting of 373 amino acid residues. MLE has two large domains and a C-terminal subdomain: an alpha + beta domain, an alpha beta-barrel domain and a C-terminal meandering subdomain. The alpha beta-barrel domain is highly irregular. Its structure is (beta/alpha)7 beta, with the structural role of the last alpha-helix being replaced by both the C-terminal subdomain and part of the N-terminal domain. The fifth, seventh and eighth barrel strands are unusual because they have left-handed twist about their axes. The strand crossing angles also vary enormously, from +9 degrees to -69 degrees; the first and last strands, which close the barrel, cross at an angle of -69 degrees, making extensive strand-strand hydrogen bonding impossible. The first barrel strand is also unusual because it starts in the N-terminal domain and forms hydrogen bonds to the C-terminal subdomain beta-sheet as well as to its neighbouring strands in the barrel. It thus cements the whole protein together. As in other alpha beta-barrel proteins, the active site of MLE, present in each subunit is at the C-terminal ends of the barrel beta-strands. The active site cleft contains an essential manganese ion, is lined with charged and other polar residues, and contains many of the crystallographic water molecules. The manganese ion is octahedrally co-ordinated to three side-chain carboxylate groups and three water molecules, and is at the centre of a radiating web of ionic and hydrogen-bonding interactions. Additionally, two water molecules are buried in the centre of the barrel and two hydrophilic side-chains (Lys167 and Arg196) make both hydrophobic and hydrophilic packing interactions with much of the barrel interior. The barrel interior is thus also unusual because it is so hydrophilic; the dominating force appears to be the need to solvate the metal ion effectively. This might account for the irregularity of the barrel. The catalytic mechanism has been investigated by docking both substrate and product in the active site with the C-COO- of muconolactone superimposed on the corresponding atoms of cis,cis-muconate. In agreement with earlier kinetic and spectroscopic results, the manganese ion does not interact directly with substrate or product.(ABSTRACT TRUNCATED AT 400 WORDS)

Crystallization↗