[Comparison on molecular characteristics of human gamma D-crystallin protein and its five mutations].
OBJECTIVE
To gain further information on the mechanisms underling the cataractogenesis by bioinformatics analysis on molecular characteristics of gamma D-crystallin (CRYGD) protein and its five cataract-associated mutations.


METHODS
With the analyzing software in bioinformatics website, we analyzed the (R14C, P23T, human wild-type CRYGD protein and the five reported mutations R36S, R58H and W156X), focusing on their physical-chemical characteristics, epitopes, post-translational modification sites, functional domains, secondary and tertiary structure.


RESULTS
R14C, R36S, R58H and W156X mutations resulted in a decrease in isoelectric point. R14C brought about a new cysteine residue exposed on the molecular surface. A decrease in local charge and a rise in local hydrophobicity was found in R14C, R36S and R58H. Local flexibility increased in P23T, while R58H caused a fall in local temperature.


CONCLUSIONS
The mutations were shown to cause changes in protein surface polarity, hydrophobicity, and spatial structure, contributing to protein deposition and cataract formation.
State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen University, Guangzhou 510060, China.
Zhenzhen
Z
Liu
Mingxing
M
Wu
D002386:Cataract / Q000235:genetics*; D019295:Computational Biology; D005838:Genotype; D006801:Humans; D008969:Molecular Sequence Data; D009154:Mutation; D038222:gamma-Crystallins / Q000145:classification / Q000235:genetics*
C504903:CRYGD protein, human; D038222:gamma-Crystallins