Publications by authors named "Zafar H Zaidi"

3 Publications

  • Page 1 of 1

Homology modeling of rho-crystallin from bullfrog (Rana catesbeiana) lens.

J Mol Graph Model 2004 Mar;22(4):285-91

Department of Biochemistry, University of Karachi, Karachi 75270, Pakistan.

rho-Crystallins are major protein component found in the eye lenses of frogs of the genus Rana. Structural analysis has indicated that frog rho-crystallins belong to aldo-keto reductase superfamily (AKRs) which include aldehyde and aldose reductases, prostaglandin F synthase and several detoxification enzymes. Members of AKRs catalyze the oxidation-reduction reaction over a range of substrates using NAD(P)(H) as a cofactor. In spite of higher structural similarity with AKRs and cofactor binding affinity, the rho-crystallins were found to be catalytically inactive. This study presents comparative or homology modeling of rho-crystallin from bullfrog (Rana catesbeiana) in presence and absence of cofactor NADP and a competitive inhibitor, testosterone. The predicted models are explored to examine the catalytic cleft, cofactor binding affinity characteristics and substrate binding pocket.
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http://dx.doi.org/10.1016/j.jmgm.2003.11.003DOI Listing
March 2004

Prediction of possible sites for posttranslational modifications in human gamma crystallins: effect of glycation on the structure of human gamma-B-crystallin as analyzed by molecular modeling.

Proteins 2003 Nov;53(2):162-73

H.E.J. Research Institute of Chemistry, International Center for Chemical Sciences, University of Karachi, Karachi, Pakistan.

Crystallins are recognized as one of the long-lived proteins of lens tissue that might serve as the target for several posttranslational modifications leading to cataract development. We have studied several such sites present in the human gamma-crystallins based either on PROSITE pattern search results or earlier experimental evidences. Their probabilities were examined on the basis of the database analysis of the gamma-crystallin sequences and on their specific locations in the constructed homology models. An N-glycosylation site in human gammaD-crystallin and several phosphorylation sites in all four human gamma-crystallins were predicted by the PROSITE search. Some of these sites were found to be strongly conserved in the gamma-crystallin sequences from different sources. An extensive analysis of these sites was performed to predict their probabilities as potential sites for protein modifications. Glycation studies were performed separately by attaching sugars to the human gammaB-crystallin model, and the effect of binding was analyzed. The studies showed that the major effect of alphaD-glucose (alphaD-G) and alphaD-glucose-6-phosphate (alphaD-G6P) binding was the disruption of charges not only at the surface but also within the molecule. Only a minor alteration in the distances of sulfhydryl groups of cysteines and on their positions in the three-dimensional models were observed, leading us to assume that glycation alone is not responsible for intra- and intermolecular disulfide bond formation.
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http://dx.doi.org/10.1002/prot.10493DOI Listing
November 2003

Homology models of human gamma-crystallins: structural study of the extensive charge network in gamma-crystallins.

Biochem Biophys Res Commun 2003 Jan;300(3):624-30

H.E.J. Research Institute of Chemistry, International Center for Chemical Sciences, University of Karachi, Karachi 75270, Pakistan.

The lens is composed of highly stable and long-lived proteins, the crystallins which are divided into alpha-, beta-, and gamma-crystallins. Human gamma-crystallins belong to the betagamma superfamily. A large number of gamma-crystallins have been sequenced and have been found to share remarkable sequence homology with each other. Some of the gamma-crystallins from various sources have also been elucidated structurally by X-ray crystallographic or NMR spectroscopic experiments. Their three-dimensional structures are also similar having consisted of two domains each possessing two Greek key motifs. In this study we have constructed the comparative or homology models of the four major human gamma-crystallins, gammaA-,gammaB-, gammaC-, and gammaD-crystallins and studied the charge network in these crystallins. Despite an overall structural similarity between these crystallins, differences in the ion pair formation do exist which is partly due to the differences in their primary sequence and partly due to the structural orientation of the neighboring amino acids. In this study, we present an elaborate analysis of these charged interactions and their formation or loss with respect to the structural changes.
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http://dx.doi.org/10.1016/s0006-291x(02)02895-4DOI Listing
January 2003