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C J De Ranter

Publications and source records attributed to C J De Ranter.

At least 19 recordsLinked to original sources
PubMed2002

Structure of an RNase-related protein from Calystegia sepium.

The structure of a catalytically inactive RNase-related protein from Calystegia sepium (CalsepRRP) has been resolved by protein crystallography at a resolution of 2.05 A and an R factor of 20.74%. Although the protein is completely devoid of ribonuclease activity, it adopts the typical alpha + beta structure of non-base-specific RNases. Analysis of the structure revealed that two amino-acid substitutions in the 'active' P1 site, in combination with the less hydrophobic/aromatic character of the B1 base-recognition site and a completely disrupted B2 base-recognition site, might account for this complete lack of activity.

Amino Acid Sequence↗
PubMed2001

Structure of a legume lectin from the bark of Robinia pseudoacacia and its complex with N-acetylgalactosamine.

The structure of the bark lectin RPbAI (isoform A4) from Robinia pseudoacacia has been determined by protein crystallography both in the free form and complexed with N-acetylgalactosamine. The free form is refined at 1.80 A resolution to an R-factor of 18.9% whereas the complexed structure has an R-factor of 19.7% at 2.05 A resolution. Both structures are compared to each other and to other available legume lectin structures. The polypeptide chains of the two structures exhibit the characteristic legume lectin tertiary fold. The quaternary structure resembles that of the Phaseolus vulgaris lectin, the soybean agglutinin, and the Dolichos biflorus lectin, but displays some unique features leading to the extreme stability of this lectin.

Acacia↗
PubMed2001

p-Formamidobenzoic acid.

The title compound, C8H7NO3, is an aromatic amide that forms an extensive hydrogen-bond network within the crystal. The crystals were obtained while preparing derivatives of benzoic acid as intermediaries in the synthesis of acridones.

Journal Article↗
PubMed2001

The crystals of a mannose-specific jacalin-related lectin from Morus nigra are merohedrally twinned.

MornigaM, a lectin from Morus nigra, belongs to the mannose-binding subgroup of the family of jacalin-related plant lectins. It was crystallized in the P6(5) space group, with unit-cell parameters a = b = 110.74, c = 159.28 A. The partially merohedrally twinned crystals could be detwinned and a subsequent molecular-replacement solution could be found using the coordinates of jacalin. Preliminary analysis clearly shows the tetrameric assembly of this protein. Furthermore, data from MornigaM crystals soaked in a mannose solution were collected.

Crystallization↗
PubMed2000

Tribenzylphosphine oxide.

The title compound, (C(6)H(5)CH(2))(3)PO, is an organic tertiary phosphine oxide. The molecule has threefold symmetry, with the P-O bond along the threefold axis. Main dimensions include P-O 1.488 (4), P-C 1.823 (3) A and O-P-C 114.7 (1) degrees. The crystals were accidentally obtained when preparing complexes of nickel(II) with dibenzylphosphine.

Journal Article↗
PubMed2000

Ethyl methyl 1,4-dihydro-4-(3-nitrophenyl)-2, 6-bis(1-piperidylmethyl)pyridine-3,5-dicarboxylate.

In the title compound, C(28)H(38)N(4)O(6), the 4-aryl substituent occupies a pseudo-axial position approximately orthogonal to the plane of the dihydropyridine ring [88.1 (3) degrees ]. The dihydropyridine ring adopts a flattened boat conformation. The H atom on the pyridine N atom is involved in a bifurcated intramolecular hydrogen bond, the acceptors being the N atoms of the two piperidylmethyl groups [N.N 2.629 (4) and 2.695 (4) A].

Journal Article↗
PubMed2000

A legume lectin from the bark of Robinia pseudoacacia crystallizes in two crystal forms: preliminary diffraction analyses.

The A(4) isoform of the bark lectin RPbAI from Robinia pseudoacacia has been crystallized in two different crystal forms. Crystal form I grows in the P2(1) space group with two tetramers in the asymmetric unit, whereas crystal form II grows in the I222 space group with a monomer in the asymmetric unit. Data sets were collected for both crystal forms to resolution limits of 2.55 and 1.81 A, respectively, which will allow successful structure determinations.

Crystallization↗
PubMed1999

Novel selective kappa-opioid ligands.

The single-crystal X-ray structures of (-)-dimethyl[(2S)-1-(5,6,7,8- tetrahydro-5-oxonaphthalene-2-acetyl)piperidin-2-ylmethyl ]ammonium chloride, C20H29N2O2+.Cl-(BRL-53001A), and (-)-ethylmethyl[(2S)-1-(5,6,7,8-tetrahydro-5-oxonaphthalene- 2- acetyl)piperidin-2-ylmethyl]-ammonium chloride dihydrate, C21H31N2O2+.Cl-.2H2O (BRL-53188A), have been determined. The two molecules have different conformations in the 1-tetralon-6-ylacetyl residue but the same conformation in the 1-acetyl-2-(dialkylaminomethyl)piperidine moiety. The conformations found are in agreement with the required chemical features for kappa affinity and antinociceptive potency.

Crystallography, X-Ray↗
PubMed1999

Plasminogen activator inhibitor 1 (PAI-1) in its active conformation: crystallization and preliminary X-ray diffraction data.

Because of its intrinsic lability, wild-type plasminogen activator inhibitor 1 (PAI-1) cannot be crystallized in its active conformation. Therefore, a stable variant of PAI-1 was used to retain the active conformation during crystallization. Four different crystallization conditions were evaluated in detail and two major types of crystals were detected. Whereas solutions consisting of either (i) cacodylate and sodium acetate, (ii) lithium sulfate and polyethylene glycol 4K, or (iii) imidazole, sodium chloride and sodium potassium phosphate buffer revealed thin platelet crystals, a solution (iv) containing ammonium acetate, citrate and polyethylene glycol 4K appeared to enhance the formation of clustered brush-like crystals. Crystals grown under condition (iii) were found to be suitable for X-ray data collection and consequent structural investigation. Data collection was 79.8% complete with a maximum resolution of 2.92 A. Importantly, PAI-1 retained its functional properties under all conditions.

Crystallization↗
PubMed1999

The structure of mouse tumour-necrosis factor at 1.4 A resolution: towards modulation of its selectivity and trimerization.

The 1.4 A resolution structure of recombinant mouse tumour-necrosis factor alpha (mTNF) at 100 K has been determined. The crystals are triclinic, space group P1, with unit-cell parameters a = 48.06, b = 48.18, c = 51.01 A, alpha = 114.8, beta = 103.6, gamma = 91.1 degrees. The structure was refined to a final crystallographic R value of 19.7% (Rfree = 23.3%), including 3477 protein atoms, one 2-propanol molecule, one Tris molecule and 240 water molecules. Throughout the crystal lattice, the trimers are differently packed compared with human TNF, which was crystallized in the tetragonal space group P41212 and refined to 2.6 A resolution. The structures of mTNF and human TNF are very similar, diverging mainly in regions that are either flexible and/or involved in crystal packing. Some loops in mTNF which contain residues important for receptor binding are better resolved than in human TNF, such as the surface-exposed loops 30-34 and 144-147, which are also important for receptor specificity. Compared with human TNFs, the channel formed by the three monomers in mTNF is narrower. One 2-propanol molecule trapped in the trimeric channel could be a lead compound for the design of TNF inhibitors.

Amino Acid Sequence↗
PubMed1997

Crystallization and preliminary X-ray studies of mouse tumor necrosis factor.

Well diffracting crystals of recombinant mouse tumor necrosis factor (mTNF) have been obtained. The sitting-drop vapor-diffusion method was used to grow crystals suitable for X-ray studies from solutions containing methoxypolyethylene glycol 2000 and isopropanol as precipitants. The crystals belong to the space group P1 with unit-cell dimensions a = 49.40, b = 48.24, c = 51.13 A, alpha = 115.06, beta = 103.32, gamma = 91.27 degrees and one trimer in the asymmetric unit. Crystals are stable to X-rays and diffract beyond 2.0 A. Cooling the crystal during data collection is necessary since crystals dissolve at room temperature.

Journal Article↗
PubMed1997

Rational design of complex formation between plasminogen activator inhibitor-1 and its target proteinases.

Considerable progress in understanding the mechanism of inhibition of proteinases by serpins has been obtained from different biochemical studies. These studies reveal that stable serpin/proteinase complex formation involves insertion of the reactive-site loop of the serpin and occurs at the acyl-enzyme stage. Even though no three-dimensional structure of a serpin/proteinase complex is resolved, structural information is available on some of the individual compounds. Molecular modeling techniques combined with recently acquired biochemical/biophysical data were used to provide insight into the stable complex formation between plasminogen activator inhibitor-1 (PAI-1) and the target proteinases: tissue-type plasminogen activator, urokinase-type plasminogen activator, and thrombin. This study reveals that PAI-1 initially interacts with its target proteinase when its reactive-site loop is solvent exposed and thereby accessible for the proteinase. Stable complex formation, however, involves the insertion of the reactive-site loop up to P7 and results in a tight binding geometry between PAI-1 and its target proteinase. The influence of different biologically relevant molecules on PAI-1/proteinase complex formation and the differences in inhibition rate constants observed for the different proteinases can be explained from these models.

Amino Acid Sequence↗
PubMed1995

Mechanisms contributing to the conformational and functional flexibility of plasminogen activator inhibitor-1.

Plasminogen activator inhibitor-1 (PAI-1) is unique among the serine proteinase inhibitors (serpins) in that it can adopt at least three different conformations (active, substrate and latent). We report the X-ray structure of a cleaved substrate variant of human PAI-1, which has a new beta-strand s4A formed by insertion of the amino-terminal portion of the reactive-site loop into beta-sheet A subsequent to cleavage. This is in contrast to the previous suggestion that the non-inhibitory function of substrate-type serpins is mainly due to an inability of the reactive-site loop to adopt this conformation. Comparison with the structure of latent PAI-1 provides insights into the molecular determinants responsible for the transition of the stressed active conformation to the thermostable latent conformation.

Amino Acid Sequence↗
PubMed1992

1-(2,3-Dideoxy-erythro-beta-D-hexopyranosyl)cytosine: an example of the conformational and stacking properties of pyranosyl pyrimidine nucleosides. A crystallographic and computational approach.

C10H15N3O4, Mr = 241.25, orthorhombic, P2(1)2(1)2(1), a = 7.4013 (4), b = 8.7563 (5), c = 17.392 (1) A, V = 1127.1 (1) A3, Z = 4, Dm = 1.42, Dx = 1.422 Mg m-3, Ni-filtered Cu K alpha radiation, lambda = 1.54178 A, mu = 0.895 mm-1, F(000) = 512, T = 293 K, final R = 0.044 for 1024 unique observed [F greater than or equal to 6 sigma (F)] reflections. The conformational parameters are in accordance with the IUPAC-IUB Joint Commission on Biochemical Nomenclature [Pure Appl. Chem. (1983), 55, 1273-1280] guidelines. In order to assess the possible use of pyranosyl-modified pyrimidine nucleosides in the design of new synthetic oligonucleotides, the conformational and packing properties of 13 structures were examined. From this study, it becomes clear that the pyrimidine-base geometry is independent of the sugar ring type (furanosyl- or pyranosyl-like). The bases are always positioned in an equatorial orientation on the pyranoside sugar, which means that the sugar adopts a 4C1 conformation in alpha- and 4C1 in beta-enantiomers. As a result of the anomeric effect the O5'-C1' bond length is 0.020 (4) A shorter than the C5'-O5' distance (C1' is the anomeric C atom). The O5'-C1'-N1-C2 torsion angle chi in the 13 nucleosides is centered around 244 (8) degrees and varies from 196.4 (3) to 287.0 (2) degrees. Molecular-mechanics calculations on uncharged pyranosyl nucleosides are found to be less accurate compared with semi-empirical quantum-chemical methods or molecular-mechanics calculations on charged molecules.(ABSTRACT TRUNCATED AT 250 WORDS)

Crystallography↗
PubMed1990

Structure of a nucleoside analogue, 3'-deoxy-3'-fluorothymidine.

1-(2,3-Dideoxy-3-fluoro-beta-D-erythro-pentofuranosyl)thymine, C10H13FN2O4, Mr = 244.22, monoclinic, P21, a = 6.408 (14), b = 18.716 (26), c = 9.329 (7) A, beta = 98.4 (1) degrees, V = 1107 (3) A3, Z = 4, Dm = 1.46, Dx = 1.465 Mg m-3, graphite-monochromated Mo K alpha radiation, lambda = 0.71073 A, mu = 0.1169 mm-1, F(000) = 512, T = 298 K, final R = 0.035 for 1425 unique observed reflections. The asymmetric unit contains two molecules (A and B). For molecule A: the N-glycosidic torsion angle chi has a value of -138.4 (5) degrees in the anti range; the sugar pucker is 2E with P = 164 (1) degrees and psi m = 36 (1) degrees and the C4'--C5' conformation is +sc with gamma = 50.2 (7) degrees. For molecule B: the N-glycosidic torsion angle chi has a value of -159.6 (5) degrees in the anti range; the sugar pucker is 2T3 with P = 169 (1) degrees and psi m = 32 (1) degrees and the C4'--C5' conformation is + sc with gamma = 52.8 (7) degrees. The conformational parameters are in accordance with the IUPAC-IUB Joint Commission on Biochemical Nomenclature [Pure Appl. Chem. (1983), 55, 1273-1280] guidelines. Base-pair formation occurs between the two molecules A and B.

Dideoxynucleosides↗
PubMed1990

Structure of the neuroleptic drug 4-amino-N-1-[(1-ethyl-2-pyrrolidinyl)methyl]-5-(ethylsulfonyl)-2- methoxybenzamide (amisulpride).

C17H27N3O4S, Mr = 369.48, monoclinic, P2(1)/c, a = 13.333 (7), b = 7.946 (4), c = 17.550 (10) A, beta = 96.99 (4) degrees, V = 1845 (2) A3, Z = 4, Dm = 1.33, Dx = 1.330 Mg m-3, graphite-monochromated Cu K alpha radiation, lambda = 1.54178 A, mu = 1.744 mm-1, F(000) = 792, T = 293 K. Final R = 0.038 for 2405 unique observed reflections. The folded conformation of the molecule with the least-squares planes of the aromatic and the pyrrolidine rings almost perpendicular is essentially determined by intra- and intermolecular hydrogen bonds. In this way, two pseudorings are formed, one linking the amide H with the methoxy O, and a second one involving the 4-amino H and a sulfonyl O. An intermolecular hydrogen bond forces the planar amide group some 28 degrees out of the plane of the aromatic ring.

Amisulpride↗
PubMed1989

Structure and absolute configuration of two stereoisomers of alpha,alpha'-[iminobis-(methylene)]bis(3,4-dihydro-2H-1-benzopyran-2- methanol) hydrobromide.

alpha,alpha'-1,1'-Bis(3,4-dihydro-2H-benzopyran-2-yl)-2,2'-iminodieth anol hydrobromide. (I) C22H28NO4+.Br-, Mr = 450.37, orthorhombic, P2(1)2(1)2(1), a = 5.1278(1), b = 13.1699(6), c = 30.858(2) A, V = 2083.9(2)A3, Z = 4, Dm = 1.44, D chi = 1.436 Mg m-3, lambda(Cu K alpha) = 1.54178 A, mu(Cu K alpha) = 2.915 mm-1, F(000) = 936, room temperature, final R = 0.054 for 2086 observed reflections. (II) C22H28NO4+.Br-, Mr = 450.37, orthorhombic, P2(1)2(1)2(1), a = 5.1292(2), b = 13.1764(9), c = 30.847(3) A, V = 2084.8(3)A3 lambda(Cu K alpha) = 1.54178A, mu(Cu K alpha) = 2.915 mm-1, F(000) = 936, room temperature, final R = 0.054 for 2676 observed reflections. The two structures are mirror images and the central C--C--N--C--C chain adopts the anti-periplanar-synclinal conformation. The active beta 1-selective adrenergic receptor blocker [isomer (I)] has the S,R,R,S absolute configuration while the inactive isomer (II) has the R,S,S,R configuration. Endless chains are formed by (N-)H...Br hydrogen bonds in the a direction and by (O-)H...Br hydrogen bonds in the b direction.

Adrenergic beta-Antagonists↗