[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.
Liu
Zhenzhen
Z
State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen University, Guangzhou 510060, China.
Wu
Mingxing
M
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