Safety and efficacy of basiliximab for the prevention of acute rejection in kidney transplant recipients.
Explore the source record for details and available documents.
Adolescent↗
Biomedical subjects
A Farooq
Publications and source records attributed to A Farooq.
Acetyl and butyrylcholinesterase-inhibiting triterpenoid alkaloids from Buxus papillosa.
Three triterpenoid alkaloids, buxakashmiramine [(20S)-20-dimethylamino-4',6'-dimethoxy-5'-hydroxybenzoylamino-3beta-methyl-buxan-31-ol] (1), buxakarachiamine [(20S)-20-dimethylamino-2'-hydroxy-3beta-methyl-3'-methyl-butanoylamino-9,10-seco-buxa-9(11), 10(19)-dien-31-ol] (2) and buxahejramine [(20S)-20-dimethylamino-2'-hydroxy-3beta-methyl-3'-methyl-pentanoylamino-9,10-seco-buxa-9(11), 10(19)-dien-31-ol] (3) were isolated from the leaves of Buxus papillosa. Four known bases, cycloprotobuxine-C (4), cyclovirobuxeine-A (5), cyclomicrophylline-A (6) and semperviraminol (7) were isolated for the first time from this species. Their structures were established through extensive spectroscopic studies. Most of these compounds exhibited anticholinesterase activity.
Acetylcholinesterase↗
Solution structure of ERK2 binding domain of MAPK phosphatase MKP-3: structural insights into MKP-3 activation by ERK2.
MAP kinases (MAPKs), which control mitogenic signal transduction in all eukaryotic organisms, are inactivated by dual specificity MAPK phosphatases (MKPs). MKP-3, a prototypical MKP, achieves substrate specificity through its N-terminal domain binding to the MAPK ERK2, resulting in the activation of its C-terminal phosphatase domain. The solution structure and biochemical analysis of the ERK2 binding (EB) domain of MKP-3 show that regions that are essential for ERK2 binding partly overlap with its sites that interact with the C-terminal catalytic domain, and that these interactions are functionally coupled to the active site residues of MKP-3. Our findings suggest a novel mechanism by which the EB domain binding to ERK2 is transduced to cause a conformational change of the C-terminal catalytic domain, resulting in the enzymatic activation of MKP-3.
Amino Acid Sequence↗
1H, 13C and 15N resonance assignments of the ERK2 binding domain of the MAPK phosphatase MKP-3.
Explore the source record for details and available documents.
Binding Sites↗
New steroidal alkaloids from Sarcococca saligna.
Five new pregnane-type steroidal alkaloids (1-5) have been isolated from Sarcococca saligna. A combination of UV, IR, MS, and 1D and 2D NMR spectroscopic studies established their structures as salignarine A [(20S)-2beta-hydroxy-4beta-acetoxy-5alpha, 6alpha-epoxy-20-(dimethylamino)-3beta-(tigloylamino)pregnane ] (1), salignarine B [(20S)-2beta-hydroxy-20-(dimethylamino)-3beta-(tigloylamino) -pregn-5- ene] (2), salignarine C [(20S)-2beta-hydroxy-20-(dimethylamino)-3beta-(senecioylamino++ +)-pregn- 5-ene] (3), salignarine D [(20S)-20-(dimethylamino)-3beta-(senecioylamino)-5alpha-preg n-16-ene] (4), and salignarine E [(20S)-20-(dimethylamino)-3beta-(tigloylamino)-pregn-4-ene] (5), respectively.
Alkaloids↗
Biotransformation of testosterone and pregnenolone catalyzed by the fungus Botrytis cinerea.
Testosterone (1), a male sex hormone, and pregnenolone (2), a precursor of many steroidal hormones, were oxidized by fermentation with the fungus Botrytis cinerea. The fermentation of 1 yielded 7beta,17beta-dihydroxyandrostan-3-one (3) (73%) in a yield comparable to chemical transformations. Fermentation of 2 by the same fungus afforded a major metabolite 3beta,11alpha, 16beta-trihydroxypregn-5-en-20-one (4) (39%) along with a minor metabolite 11alpha,16beta-dihydroxypregn-4-ene-3,20-dione (5) (6%). The metabolites are characterized by detailed physical and spectroscopic studies.
Biotransformation↗
Phosphotyrosine binding domains of Shc and insulin receptor substrate 1 recognize the NPXpY motif in a thermodynamically distinct manner.
Phosphotyrosine binding (PTB) domains of the adaptor protein Shc and insulin receptor substrate (IRS-1) interact with a distinct set of activated and tyrosine-phosphorylated cytokine and growth factor receptors and play important roles in mediating mitogenic signal transduction. By using the technique of isothermal titration calorimetry, we have studied the thermodynamics of binding of the Shc and IRS-1 PTB domains to tyrosine-phosphorylated NPXY-containing peptides derived from known receptor binding sites. The results showed that relative contributions of enthalpy and entropy to the free energy of binding are dependent on specific phosphopeptides. Binding of the Shc PTB domain to tyrosine-phosphorylated peptides from TrkA, epidermal growth factor, ErbB3, and insulin receptors is achieved via an overall entropy-driven reaction. On the other hand, recognition of the phosphopeptides of insulin and interleukin-4 receptors by the IRS-1 PTB domain is predominantly an enthalpy-driven process. Mutagenesis and amino acid substitution experiments showed that in addition to the tyrosine-phosphorylated NPXY motif, the PTB domains of Shc and IRS-1 prefer a large hydrophobic residue at pY-5 and a small hydrophobic residue at pY-1, respectively (where pY is phosphotyrosine). These results agree with the calculated solvent accessibility of these two key peptide residues in the PTB domain/peptide structures and support the notion that the PTB domains of Shc and IRS-1 employ functionally distinct mechanisms to recognize tyrosine-phosphorylated receptors.
Adaptor Proteins, Signal Transducing↗
Mononuclear cell-modulation of granulosa cell steroidogenesis in rat: influence of ovarian cycle.
The mononuclear cells exert a paracrine influence on the ovarian function, including steroidogenesis. This study examines the ability of the conditioned medium from the cultures of splenic mononuclear cells, obtained during various phases of the ovarian cycle, on progesterone accumulation by the granulosa cells in the culture medium. Female Wistar rats, aged twenty-five days, were made pseudopregnant by an injection of pregnant mare's serum gonadotropin. The splenic mononuclear cells were isolated at follicular phase, early luteal phase, mid luteal phase and late luteal phase and cultured for 48 h. The ammonium sulphate precipitated fraction of the conditioned medium was added to the granulosa cells obtained from immature rats treated with diethylstillboestrol. The granulosa cells were cultured for 48 h, and the progesterone accumulated in the medium was assayed. The conditioned medium from the cultures of the mononuclear cells obtained during follicular phase and late luteal phase inhibited FSH-induced progesterone secretion, whereas conditioned medium obtained from mid luteal phase mononuclear cells enhanced the effect of FSH. The stimulatory effect of db-cAMP on progesterone accumulation in the culture medium is inhibited by conditioned medium obtained from all the phases of the ovarian cycle. This study demonstrates a cyclicity in the behaviour of the splenic mononuclear cells on ovarian steroidogenesis, suggesting a bi-directional paracrine and/or endocrine relationship between ovary and the mononuclear cells.
Animals↗
Magnetic resonance imaging evaluation of thecal sac diameters following laminectomy in the lumbar spine.
Sagittal magnetic resonance images (MRIs) from 20 patients who had postoperative persistent or recurrent low back pain were reviewed to study the thecal sac diameter at laminectomy sites. The thecal sac anteroposterior diameter was measured in three sites: the maximum AP diameter at the laminectomy site, and the proximal and distal levels to the laminectomy site. A comparison between the thecal sac AP diameter at laminectomy sites and the average diameter of both the proximal and distal levels was then made. Based on the measurements, the diameters of the thecal sac were divided into three groups. Patients in group A (5 cases) had a constriction (the thecal sac AP diameter at the laminectomy site was less than the average diameter of both the proximal and distal levels) of the thecal sac at the laminectomy site. Patients in group B (12 cases) had an expansion (the thecal sac AP diameter at the laminectomy site was more than the average diameter of both the proximal and distal levels) of the thecal sac. Patients in group C (3 cases) demonstrated no change. This study suggests that there was no correlation between the thecal sac AP diameter at laminectomy site and postoperative low back pain.
Adolescent↗
Distribution of AB0 and RH blood group alleles in different populations of southern Punjab, Pakistan.
The analysis of a sample of 1632 individuals from patients of the Nishtar Teaching Hospital, Multan, suggests that different ethnic groups (Araeen, Mughals, Syed, Jat, Rajputs, Baloch and Pathan) are not significantly different from another with regard to the distribution of RH blood group alleles (RH*d around 0.30). The distributions of the AB0 blood group alleles suggest that different ethnic groups are not significantly different from the average alele frequencies (AB0*A = 0.23, AB0*B = 0.33, AB0*0 = 0.47) except for the Pathan ethnic group (AB0*A = 0.35, AB0*B = 0.47, AB0*0 = 0.27). The populations of different geographic areas are not significantly different from the average allele frequencies, except for the southern district of Rahim Yar Khan (AB0*A = 0.12) and the northern district of Sahiwal (AB0*A = 0.19). The populations of Sahiwal (RH*d = 0.35) and Muzaffargarh (RH*d = 0.36) yield significantly different allele frequencies at the RH locus. The interpopulation differences can be explained by the geographic distance. There is a significant difference in the frequencies of the AB0 alleles between rural and urban populations, suggesting that rural populations maintain their isolation from urban populations. Rural and urban populations are not significantly different from one another concerning the allele frequencies at the RH locus.
ABO Blood-Group System↗
Kinetic evidence for an obligatory intermediate in the folding of the membrane protein bacteriorhodopsin.
A photodiode array in conjunction with a rapid stopped-flow mixing method, with a millisecond time resolution, is used here to study the refolding of the membrane protein bacteriorhodopsin from an apoprotein state with a native-like secondary structure in mixed phospholipid/detergent micelles. Refolding to the native state is initiated by the rapid mixing of all-trans-retinal and the apoprotein bacterioopsin in mixed micelles. A lag phase of several seconds is observed in the appearance of the native state, as monitored by the increase in absorbance of the native chromophore. This observation demonstrates unequivocally that an intermediate is obligatory in the formation of bacteriorhodopsin. It is further shown that this intermediate is spectroscopically distinct from free retinal (absorbance maximum approximately 380 nm) and bacteriorhodopsin (absorbance maximum approximately 560 nm) and absorbs maximally at 430 nm. Evidence for the decay of the 430 nm intermediate into bacteriorhodopsin via three distinct parallel pathways is also provided. Taken together, these findings are used to describe a model in which distinct populations of the apoprotein in mixed micelles appear to fold along separate pathways via their corresponding intermediates into the native state. How the results of this study provide new insights into the mechanisms of protein folding is discussed.
Apoproteins↗
Antibacterial steroidal alkaloids from Sarcococca saligna.
Two new pregnane-type steroidal alkaloids, saligcinnamide [(20S,2'E)-20-(N,N-dimethylamino)-3beta-(3'-phenyl-2'-propenyl-N-meth ylamido)pregnane](1) and N(a)-methyl epipachysamine-D [(20S)-20-(N,N-dimethylamino)-3beta-(N-methylbenzamido)pregnane](2 ), along with a known base, epipachysamine D [(20S)-20-(N,N-dimethylamino)-3beta-(benzamido)pregnane] (3), were isolated from the EtOH extracts of the roots and stems of Sarcococca saligna. The new bases exhibited antibacterial activity against several human pathogenic bacteria. Two derivatives of 1, dihydrosaligcinnarnide [(20S)-20-(N,N-dimethylamino)-3beta-(3'-phenylpropionoyl-N-meth ylamido)pregnane](4) and dihydrosaligcinnamine [(20S)-20-(N,N-dimethylamino)-3beta-N-(3'-phenylpropyl-N-methylamino)pre gnane](5), and a derivative of 2, N(a)-methyl epipachysamine [(20S)-20-(N,N-dimethylamino)-3beta-(N-benzyl,N-methylamino)pregnane](6) were prepared and their antibacterial activity determined.
Alkaloids↗
Fungal transformation of (1R,2S,5R)-(-)-menthol by cephalosporiumaphidicola
Incubation of (1R,2S,5R)-(-)-menthol (1) with Cephalosporium aphidicola for 12 days yielded the six oxidized metabolites: 10-acetoxymenthol (2), 7-hydroxymenthol (3), 4alpha-hydroxymenthol (4), 3alpha-hydroxymenthol (5), 9-hydroxymenthol (6), and 10-hydroxymenthol (7). The structures of the novel compounds 2, 4, 5, and 7 were assigned by interpretation of their spectral data.
Journal Article↗
Structure-activity relationships of imperialine derivatives and their anticholinergic activity.
In order to check the structure-activity relationship and prepare more potent derivatives of imperialine with anticholinergic activity, imperialinol (2), 3 beta-acetoxyimperialine (3), 3 beta-propionoxyimperialine (4), and 3 beta-butyroxyimperialine (5) were prepared. Compounds 4 and 5 displayed better anticholinergic activity against muscarinic receptors of the heart and brain than imperialine (1). The decrease in activity in 2 showed the importance of the 6-keto functionality in imparting the anticholinergic activity.
Alkaloids↗
Intermediates in the assembly of bacteriorhodopsin investigated by time-resolved absorption spectroscopy.
The in vitro folding and assembly kinetics of bacteriorhodopsin have been studied by absorption spectroscopy. Folding is initiated by rapid stopped-flow mixing of denatured apoprotein (bacterio-opsin) in SDS micelles and mixed dimyristoylglycerophosphocholine/Chaps micelles containing retinal. The apparent mixing rate of the two types of micelles has been determined by time-resolving the changes in light scattering by the micelles. Micelle mixing appears to occur in two stages: a fast phase with an apparent rate constant of about 420 s-1, and a second phase with an apparent rate constant of about 10 s-1. A rate constant of similar magnitude to the latter has previously been assigned to a protein-folding event on the basis of protein fluorescence studies [Booth, P. J., Farooq, A. & Flitsch, S. L. (1996) Biochemistry 35, 5902-5909]. However the results presented here show that this rate constant may be associated with a rearrangement of the mixed detergent/lipid micelles. When the changes in the retinal absorption band are time-resolved during assembly of bacteriorhodopsin, a retinal-protein intermediate, with an absorption maximum of about 430 nm, has been identified. This absorption maximum lies between that of unbound retinal (at about 380 nm) and the native chromophore (at about 560 nm). A comparison of fluorescence and absorption data, together with previous evidence [Booth, P. J., Flitsch, S. L., Stern, L. J., Greenhalgh, D. A., Kim, P. S., & Khorana, H. G. (1995) Nat. Struct. Biol. 2, 139-143], suggests that the covalent Schiff-base link to retinal is not formed in the 430-nm-absorbing intermediate.
Bacteriorhodopsins↗
Evidence that bilayer bending rigidity affects membrane protein folding.
The regeneration kinetics of the integral membrane protein bacteriorhodopsin have been investigated in a lipid-based refolding system. Previous studies on bacteriorhodopsin regeneration have involved detergent-based systems, and in particular mixed dimyristoylphosphatidylcholine (DMPC)/CHAPS micelles. Here, we show that the short chain lipid dihexanoylphosphatidylcholine (DHPC) can be substituted for the detergent CHAPS and that bacteriorhodopsin can be regenerated to high yield in mixed DMPC/DHPC micelles. Bacteriorhodopsin refolding kinetics are measured in the mixed DMPC/DHPC micelles. Rapid, stopped flow mixing is employed to initiate refolding of denatured bacterioopsin in SDS micelles with mixed DMPC/DHPC micelles and time-resolved fluorescence spectroscopy to follow changes in protein fluorescence during folding. Essentially identical refolding kinetics are observed for mixed DMPC/CHAPS and mixed DMPC/DHPC micelles. Only one second-order retinal/apoprotein reaction is identified, in which retinal binds to a partially folded apoprotein intermediate, and the free energy of this retinal binding reaction is found to be the same in both types of mixed micelles. Formation of the partially folded apoprotein intermediate is a rate-limiting step in protein folding and appears to be biexponential. Both apparent rate constants are found to be dependent on the relative proportion of DMPC present in the mixed DMPC/DHPC micelles as well as on the pH of the aqueous phase. Increasing the DMPC concentration should increase the bending rigidity of the amphiphilic bilayer, and this is found to slow the rate of formation of the partially folded apoprotein intermediate. Increasing the mole fraction of DMPC from 0.3 to 0.6 slows the two apparent rate constants associated with formation of this intermediate from 0.29 and 0.031 to 0.11 and 0.013 s-1, respectively. Formation of the intermediate also slows with increasing pH, from 0.11 and 0.013 s-1 at pH 6 to 0.033 and 0.0053 s-1 at pH 8. Since this pH change has no known effect on the phase behavior of lecithins, this is more likely to represent a direct effect on the protein itself. Thus, it appears to be possible to control the rate-limiting process in bacterioopsin folding through both bilayer bending rigidity and pH.
Bacteriorhodopsins↗
Two new pregnane-type steroidal alkaloids from Sarcococca saligna.
Two new preganae-type steroidal alkaloids, (20S, 2'Z)-20- (N,N-dimethylamino)-3 beta-(2-methyl-2Z-butenamido)-pregn-5-en-4-one and (20S, 2'Z)-20-(N,N-dimethylamino)-3 beta-(2-methyl-2Z-butenamido)- pregna-5,14-dien-4-one, have been isolated from an ethanolic extract of the roots and stems of Sarcococca saligna, in addition to the two known alkaloids, N-formylchonemorphine and vaganine-A, which have been isolated for the first time from this species.
Anti-Infective Agents↗
Microbial transformation of sclareolide.
The microbial transformation of sclareolide (1) by Curvularia lunata afforded five oxidized metabolites identified as 3-ketosclareolide (2), 1 beta-hydroxysclareolide (3), 3 beta-hydroxysclareolide (4), 1 alpha,3 beta-dihydroxysclareolide (5), and 1 beta, 3 beta-dihydroxysclareolide (6). Fermentations of 1 with Aspergillus niger also produced metabolites 2-6. Metabolites 2-5 were obtained by fermention with Gibberella fujikuroii, while fermentation with Fusarium lini afforded metabolites 4 and 5.
Agaricales↗