Molecular signatures of Calpain 10 isoforms sequences, envisage functional similarity and therapeutic potential.

Abstract

Calpain 10 plays a role in insulin secretion, action and susceptibility to type 2 diabetes. The mechanism through which it influences the insulin secretion and action is not completely defined. A structural bioinformatics approach is applied to envision its mechanism of action using available tools on NCBI (blastp and blastn), EMBL-EBI, Ensembl, Swiss Model Repository websites, I-TASSER, PROCHECK program and Discovery Studio software. Homology of domain I and II of calpain10 (isoform a) was established with super family cysteine proteinase domains (II a and II b, e=1.30e-77, 1.00e-20). Remaining sequences of domain III and T from (isoform a and c) indicated some similarity (Avg. e=1.94e-37) to calpain large subunit domain III (PF01067), the isoform g (139 AA) showed similarity with a part of catalytic domain of cysteine protease super family (e-value 1.00e-20). Swiss-model repository for 3D structures of protein, showed structural resemblance of 29% with 1QXP template of mu-calpain, 27% with 1KFX of m-calpain and 32% with 2P0R of calpain 9 in complex with leupeptin. Models prepared through I-TASSER confirmed through Ramachandran (RC) plots. The calpain 10 isoforms a, c and g show partial structural and functional resemblance to m, mu and calpain 9. This information is useful to find new drugs for disease management.

• Authors: Bushra Chaudhry, Farina Hanif, Kausar Saboohi
• Journal: Pakistan journal of pharmaceutical sciences (Pak J Pharm Sci) Vol. 32 Issue 3 Pg. 937-946 (May 2019) ISSN: 1011-601X [Print] Pakistan
• PMID: 31278703 (Publication Type: Journal Article)

Chemical References

• Protein Isoforms
• Calpain
• calpain 10

Topics

• Calpain (chemistry, genetics, metabolism)
• Computational Biology (methods)
• Humans
• Models, Molecular
• Protein Conformation
• Protein Domains
• Protein Isoforms (chemistry, genetics, metabolism)
• Sequence Alignment