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Conserved water-mediated recognition and dynamics of NAD(+) (carboxamide group) to hIMPDH enzyme: water mimic approach toward the design of isoform-selective inhibitor

Bairagya, Hridoy R and Mishra, Deepak K and Mukhopadhyay, Bishnu P and Sekar, K (2014) Conserved water-mediated recognition and dynamics of NAD(+) (carboxamide group) to hIMPDH enzyme: water mimic approach toward the design of isoform-selective inhibitor. In: JOURNAL OF BIOMOLECULAR STRUCTURE & DYNAMICS, 32 (8). pp. 1248-1262.

Full text not available from this repository.
Official URL: http://dx.doi.org/10.1080/07391102.2013.812982

Abstract

Inosine monophosphate dehydrogenase (IMPDH) enzyme involves in GMP biosynthesis pathway. Type I hIMPDH is expressed at lower levels in all cells, whereas type II is especially observed in acute myelogenous leukemia, chronic myelogenous leukemia cancer cells, and 10 ns simulation of the IMP-NAD(+) complex structures (PDB ID. 1B3O and 1JCN) have revealed the presence of a few conserved hydrophilic centers near carboxamide group of NAD(+). Three conserved water molecules (W1, W, and W1 `) in di-nucleotide binding pocket of enzyme have played a significant role in the recognition of carboxamide group (of NAD(+)) to D274 and H93 residues. Based on H-bonding interaction of conserved hydrophilic (water molecular) centers within IMP-NAD(+)-enzyme complexes and their recognition to NAD(+), some covalent modification at carboxamide group of di-nucleotide (NAD(+)) has been made by substituting the -CONH(2)group by -CONHNH2 (carboxyl hydrazide group) using water mimic inhibitor design protocol. The modeled structure of modified ligand may, though, be useful for the development of antileukemic agent or it could be act as better inhibitor for hIMPDH-II.

Item Type: Journal Article
Additional Information: Copyright for this article belongs to TAYLOR & FRANCIS INC, USA.
Keywords: NAD+;conserved water molecules;inhibitor;hIMPDH-I and II; recognition;isoform-specific;modified NAD+
Department/Centre: Division of Information Sciences > Supercomputer Education & Research Centre
Depositing User: Id for Latest eprints
Date Deposited: 10 Jun 2014 10:58
Last Modified: 10 Jun 2014 10:58
URI: http://eprints.iisc.ac.in/id/eprint/49112

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