Conserved Water Mediated H-bonding Dynamics of Inhibitor, Cofactor, Asp 364 and Asn 303 in Human IMPDH II

被引：28

作者：

Bairagya, Hridoy R. ^{[1
]}

Mukhopadhyay, Bishnu P. ^{[1
]}

Sekarz, K. ^{[2
]}

机构：

[1] Natl Inst Technol Durgapur, Dept Chem, W Bengal 713209, Durgapur, India

[2] Indian Inst Sci, Bioinformat Ctr, Bangalore 560012, Karnataka, India

来源：

JOURNAL OF BIOMOLECULAR STRUCTURE & DYNAMICS | 2009年 / 26卷 / 04期

关键词：

IMPDH II; Molecular Dynamics; Inhibitor; INOSINE MONOPHOSPHATE DEHYDROGENASE; PROTEIN DATA-BANK; MOLECULAR-DYNAMICS; CRYSTAL-STRUCTURE; 5'-MONOPHOSPHATE DEHYDROGENASE; ACTIVE-SITE; COMPLEX; CONFORMATION; SIMULATIONS; CHANNELS;

D O I：

10.1080/07391102.2009.10507265

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

The IMPDH (Inosine monophosphate dehydrogenase)-II is largely produced in cancer cells. Extensive MD-simulation (2 ns) of the 11330, 1NFB, 1NF7, 1LRT, and I MEW PDB-structures revealed the presence of a conserved water molecule, which is H-bonded and stabilized by the surrounding ribose hydroxyl (O2) of inhibitor, nitrogen (NN) of cofactor, carboxyl oxygen (OD2) and amide nitrogen atoms of the active site Asp 364 and Asn 303 of human. These water-mediated interaction are partially supported in the solvated and X-ray structures. The stereochemistry of the four- centered H-bonds around the conserved water center may be exploited to design a better model inhibitor for IMPDH-II.

引用

页码：497 / 507

页数：11

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