PDBsum entry 1mz3

Structural protein

PDB id: 1mz3

Contents

Protein chain

174 a.a.

Ligands

G6P ×2

Theoretical model

PDB id:

1mz3

Name:

Structural protein

Title:

Homology model of human gamma-b-crystallin bound with two molecules of alpha-d-glucose-6-phosphate each at gly1 and lys2

Structure:

Gammab crystallin. Chain: a. Synonym: gamma crystallin b

Source:

Homo sapiens. Human

Authors:

A.Salim,A.Bano,Z.H.Zaidi

Key ref:

A.Salim et al. (2003). 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, 53, 162-173. PubMed id: 14517968 DOI: 10.1002/prot.10493

Date:

05-Oct-02 Release date: 30-Oct-02

Protein chain

P07316  (CRGB_HUMAN) -  Gamma-crystallin B

Seq: 175 a.a.

Struc: 174 a.a.*

* PDB and UniProt seqs differ at 1 residue position (black cross)

DOI no: 10.1002/prot.10493

Proteins 53:162-173 (2003)

PubMed id: 14517968

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.

A.Salim, A.Bano, Z.H.Zaidi.

ABSTRACT

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.

Selected figure(s)

Figure 1.
Figure 1. CLUSTAL W multiple-sequence alignment of -crystallin sequences from human, bovine, rat, and mouse retrieved from the SWISS PROT data bank. Predicted patterns containing specific sites for posttranslational modifications in -crystallin are highlighted. Not all of these sites identified by the PROSITE search were conserved throughout the sequence. Sites that are strongly conserved in the database of -crystallin sequences are marked by arrows.

Figure 3.
Figure 3. Possible phosphorylation sites (shown in ball and stick) as predicted by their positions in the homology models (a) human A-crystallin: Ser87, Tyr98, Tyr154, and Thr171; (b) human C-crystallin: Tyr65 and Ser87; and (c) human D-crystallin: Ser87 and Tyr98.

The above figures are reprinted by permission from John Wiley & Sons, Inc.: Proteins (2003, 53, 162-173) copyright 2003.

Figures were selected by an automated process.