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1.
Epitope analysis and molecular modeling reveal the topography of the C-terminal peptide of the beta-subunit of human chorionic gonadotropin. 总被引:2,自引:0,他引:2
N Venkatesh S Krishnaswamy S Meuris G S Murthy 《European journal of biochemistry》1999,265(3):1061-1066
Human chorionic gonadotropin (hCG) belongs to a family of heterodimeric glycoprotein hormones that share a common alpha-subunit and a hormone-specific beta-subunit. Among the gonadotropin beta-subunits, greater than 85% homology exists between lutropin (hLH)beta and hCGbeta in their first 114 amino acid residues. However, unlike hLHbeta, hCGbeta contains a 31-amino acid hydrophilic stretch at its carboxyl end (CTPbeta: C-terminal peptide). Although the crystal structure of deglycosylated hCG has been solved, the topography of CTPbeta remains unknown. In this study, we have attempted to define the topology of CTPbeta using mAb probes. We investigated three epitopes on hCGalpha, which are hidden in the hCGalphabeta dimer. However, these epitopes are not hidden in hLH, which has a similar subunit interface to that of hCG, but lacks CTPbeta. This suggested that these epitopes are not masked at the subunit interface of hLH or hCG. Hence, we hypothesized that, in the case of hCG, these epitopes are masked by the CTPbeta. Consistent with this view, several treatments of hCG that removed CTPbeta unmasked these epitopes and enhanced their reactivity with the corresponding mAbs. In order to localise the position of CTPbeta on the alpha-subunit, we used an epitope-mapping strategy [N. Venkatesh & G. S. Murthy (1997) J. Immunol. Methods 202, 173-182] based on differential susceptibility of epitopes to covalent modifications. This enabled us to predict the possible topography of CTPbeta. Further, we were also able to build a model of CTPbeta, completely independently of the epitope-mapping studies, using a homology-based modeling approach [S. Krishnaswamy, I. Lakshminarayanan & S. Bhattacharya (1995) Protein Sci. 4 (Suppl. 2), 86-97]. Results obtained from these two different approaches (epitope analysis and homology modeling) agree with each other and indicate that portions of CTPbeta are in contact with hCGalpha in the native hCG dimer. 相似文献
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B R Deshpande V L Kallapur K Venkatesh 《Archives internationales de physiologie et de biochimie》1984,92(2):65-72
The quantitative determination of succinic dehydrogenase (SDH), hexokinase (HK), phosphorylase, phosphofructokinase (PFK), glycerol-3-phosphate dehydrogenase (G-3-PDH) and lactate dehydrogenase (LDH) was carried out in the homologous leg muscles of two aquatic Birds. It appears that the leg muscle fibres of the coot, a surface swimmer are more oxidative in nature and appear to utilize glucose as source of energy. The leg muscles of the dabchick, a diving Bird, on the other hand, seem to depend on glycogen as source of energy. The relative activity levels of HK, phosphorylase and PFK support the accepted r?le of glycogen as primary substrate of carbohydrate catabolism in the leg muscles. The ratio of G-3-PDH/LDH in the leg muscles revealed that glycerol 3-phosphate cycle appears to be insufficient to account for the major part of NADH oxidation. However, the LDH activity is quite high in all the muscles. These results led us to believe that glycerol 3-phosphate cycle may function during rest, when the rate of glycolysis will be low. 相似文献
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K Venkatesh Y A Abdel-Aal F B Armstrong R M Roe 《The Journal of biological chemistry》1990,265(35):21727-21732
Juvenile hormone (JH) esterase found primarily in the hemolymph and tissues of insects is a low abundance protein involved in the ester hydrolysis of insect juvenile hormones, JHs. The enzyme was purified from the larval plasma of wild-type Manduca sexta using an affinity column prepared by binding the ligand, 3-[(4'-mercapto)butylthio]-1,1,1-trifluoropropan-2-one (MBTFP), to epoxy-activated Sepharose. The purification was greater than 700-fold with a 72% recovery, and the purified enzyme appeared as a single protein on sodium dodecyl sulfate-polyacrylamide gel electrophoresis, immunoelectrophoresis, reverse phase high performance liquid chromatography, and amino acid sequence analysis. The molecular weight was 66,000. The plasma JH esterase in wild-type, black, and white strains of M. sexta was similar when analyzed by immunotitration, wide range (pH 3.5-9.0) isoelectric focusing, and inhibition with MBTFP and 3-octylthio-1,1,1-trifluoropropan-2-one (OTFP). Inhibition studies revealed a sensitive and insensitive form (I50 = 10(-9) and 10(-6) M, respectively) in these three biotypes. Narrow range isoelectric focusing (pH 4.0-7.0) indicated the presence of two major isoelectric forms with pI values of 6.0 and 5.5, but their inhibition kinetics with OTFP and O,O-diisopropyl phosphorofluoridate were identical. 相似文献
6.
The bulbous tubular portion of the median ejaculatory duct functions as the accessory gland in the male stable fly, Stomoxys calcitrans. The gland started to enlarge after emergence when the fly was fed on sugar-water or blood. Implants of accessory glands from sugar-water or blood-fed males were effective in stimulating oviposition in virgin females. The injection into females of accessory-gland extracts from males fed blood prevented insemination; this extract was effective in concentration as low as 0.25 gland per female. Accessory-gland extracts from sugar-water fed males were only partially effective in preventing female insemination. However, the accessory-gland extracts of male stable flies had little effect on insemination when injected into three other species of female dipterans.Spermatogenesis was completed by the time of emergence, or shortly thereafter, a process independent of blood feeding. Three types of spermatids were identified, forming a continuum of spermiogenesis stages. Fat, fusiform spermatozoa elongated to become thin, elongate and mature spermatozoa. 相似文献
7.
Sebastian Swanson Venkatesh Sivaraman Gevorg Grigoryan Amy E. Keating 《Protein science : a publication of the Protein Society》2022,31(6)
Despite advances in protein engineering, the de novo design of small proteins or peptides that bind to a desired target remains a difficult task. Most computational methods search for binder structures in a library of candidate scaffolds, which can lead to designs with poor target complementarity and low success rates. Instead of choosing from pre‐defined scaffolds, we propose that custom peptide structures can be constructed to complement a target surface. Our method mines tertiary motifs (TERMs) from known structures to identify surface‐complementing fragments or “seeds.” We combine seeds that satisfy geometric overlap criteria to generate peptide backbones and score the backbones to identify the most likely binding structures. We found that TERM‐based seeds can describe known binding structures with high resolution: the vast majority of peptide binders from 486 peptide‐protein complexes can be covered by seeds generated from single‐chain structures. Furthermore, we demonstrate that known peptide structures can be reconstructed with high accuracy from peptide‐covering seeds. As a proof of concept, we used our method to design 100 peptide binders of TRAF6, seven of which were predicted by Rosetta to form higher‐quality interfaces than a native binder. The designed peptides interact with distinct sites on TRAF6, including the native peptide‐binding site. These results demonstrate that known peptide‐binding structures can be constructed from TERMs in single‐chain structures and suggest that TERM information can be applied to efficiently design novel target‐complementing binders. 相似文献
8.
Sundarapandian Thangapandian Shalini John Yuno Lee Venkatesh Arulalapperumal Keun Woo Lee 《PloS one》2012,7(11)
Histone deacetylases (HDACs) have emerged as effective therapeutic targets in the treatment of various diseases including cancers as these enzymes directly involved in the epigenetic regulation of genes. However the development of isoform-selective HDAC inhibitors has been a challenge till date since all HDAC enzymes possess conserved tunnel-like active site. In this study, using molecular dynamics simulation we have analyzed the behavior of tunnels present in HDAC8, 10, and 11 enzymes of class I, II, and IV, respectively. We have identified the equivalent tunnel forming amino acids in these three isoforms and found that they are very much conserved with subtle differences to be utilized in selective inhibitor development. One amino acid, methionine of HDAC8, among six tunnel forming residues is different in isoforms of other classes (glutamic acid (E) in HDAC10 and leucine (L) in HDAC 11) based on which mutations were introduced in HDAC11, the less studied HDAC isoform, to observe the effects of this change. The HDAC8-like (L268M) mutation in the tunnel forming residues has almost maintained the deep and narrow tunnel as present in HDAC8 whereas HDAC10-like (L268E) mutation has changed the tunnel wider and shallow as observed in HDAC10. These results explained the importance of the single change in the tunnel formation in different isoforms. The observations from this study can be utilized in the development of isoform-selective HDAC inhibitors. 相似文献
9.
Chiu-Hao Chen Sai Venkatesh Pingali Shekhar Garde Mark L. Schlossman 《Biophysical journal》2009,97(10):2794-2802
X-ray reflectivity measurements are used to determine the configuration of the C2 domain of protein kinase Cα (PKCα-C2) bound to a lipid monolayer of a 7:3 mixture of 1-stearoyl-2-oleoyl-sn-glycero-3-phosphocholine and 1-stearoyl-2-oleoyl-sn-glycero-3-phosphoserine supported on a buffered aqueous solution. The reflectivity is analyzed in terms of the known crystallographic structure of PKCα-C2 and a slab model representation of the lipid layer. The configuration of lipid-bound PKCα-C2 is described by two angles that define its orientation, θ = 35° ± 10° and φ =210° ± 30°, and a penetration depth (=7.5 ± 2 Å) into the lipid layer. In this structure, the β-sheets of PKCα-C2 are nearly perpendicular to the lipid layer and the domain penetrates into the headgroup region of the lipid layer, but not into the tailgroup region. This configuration of PKCα-C2 determined by our x-ray reflectivity is consistent with many previous findings, particularly mutational studies, and also provides what we believe is new molecular insight into the mechanism of PKCα enzyme activation. Our analysis method, which allows us to test all possible protein orientations, shows that our data cannot be explained by a protein that is orientated parallel to the membrane, as suggested by earlier work. 相似文献
10.