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Comprehensive analysis of the Co-structures of dipeptidyl peptidase IV and its inhibitor.

ABSTRACT: We comprehensively analyzed X-ray cocrystal structures of dipeptidyl peptidase IV (DPP-4) and its inhibitor to clarify whether DPP-4 alters its general or partial structure according to the inhibitor used and whether DPP-4 has a common rule for inhibitor binding.All the main and side chains in the inhibitor binding area were minimally altered, except for a few side chains, despite binding to inhibitors of various shapes. Some residues (Arg125, Glu205, Glu206, Tyr662 and Asn710) in the area had binding modes to fix a specific atom of inhibitor to a particular spatial position in DPP-4. We found two specific water molecules that were common to 92 DPP-4 structures. The two water molecules were close to many inhibitors, and seemed to play two roles: maintaining the orientation of the Glu205 and Glu206 side chains through a network via the water molecules, and arranging the inhibitor appropriately at the S2 subsite.Our study based on high-quality resources may provide a necessary minimum consensus to help in the discovery of a novel DPP-4 inhibitor that is commercially useful.

SUBMITTER: Nojima H

PROVIDER: S-EPMC4974693 | biostudies-literature | 2016 Aug

REPOSITORIES: biostudies-literature

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Comprehensive analysis of the Co-structures of dipeptidyl peptidase IV and its inhibitor.

Nojima Hiroyuki H Kanou Kazuhiko K Terashi Genki G Takeda-Shitaka Mayuko M Inoue Gaku G Atsuda Koichiro K Itoh Chihiro C Iguchi Chie C Matsubara Hajime H

BMC structural biology 20160805

<h4>Background</h4>We comprehensively analyzed X-ray cocrystal structures of dipeptidyl peptidase IV (DPP-4) and its inhibitor to clarify whether DPP-4 alters its general or partial structure according to the inhibitor used and whether DPP-4 has a common rule for inhibitor binding.<h4>Results</h4>All the main and side chains in the inhibitor binding area were minimally altered, except for a few side chains, despite binding to inhibitors of various shapes. Some residues (Arg125, Glu205, Glu206, T ...[more]

PMID: 27491540

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Comprehensive analysis of the Co-structures of dipeptidyl peptidase IV and its inhibitor.

Publications

Comprehensive analysis of the Co-structures of dipeptidyl peptidase IV and its inhibitor.

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