L337H mutant of rat neuronal nitric oxide synthase resembles human neuronal nitric oxide synthase toward inhibitors

Jianguo Fang; Haitao Ji; Graham R. Lawton; Fengtian Xue; Linda J. Roman; Richard B. Silverman

doi:10.1021/jm900380j

L337H mutant of rat neuronal nitric oxide synthase resembles human neuronal nitric oxide synthase toward inhibitors

Jianguo Fang, Haitao Ji, Graham R. Lawton, Fengtian Xue, Linda J. Roman, Richard B. Silverman

Chemistry

Research output: Contribution to journal › Article › peer-review

13 Scopus citations

Abstract

A common dichotomy exists in inhibitor design: should the compounds be designed to block the enzymes of animals in the preclinical studies or to inhibit the human enzyme? We report that a single mutation of Leu-337 in rat neuronal nitric oxide synthase (nNOS) to His makes the enzyme resemble human nNOS more than rat nNOS. We expect that the approach used in this study can unite the dichotomy and speed up the process of inhibitor design and development.

Original language	English (US)
Pages (from-to)	4533-4537
Number of pages	5
Journal	Journal of Medicinal Chemistry
Volume	52
Issue number	14
DOIs	https://doi.org/10.1021/jm900380j
State	Published - Jul 23 2009

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ASJC Scopus subject areas

Drug Discovery
Molecular Medicine

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10.1021/jm900380j

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abstract = "A common dichotomy exists in inhibitor design: should the compounds be designed to block the enzymes of animals in the preclinical studies or to inhibit the human enzyme? We report that a single mutation of Leu-337 in rat neuronal nitric oxide synthase (nNOS) to His makes the enzyme resemble human nNOS more than rat nNOS. We expect that the approach used in this study can unite the dichotomy and speed up the process of inhibitor design and development.",

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AU - Ji, Haitao

AU - Lawton, Graham R.

AU - Xue, Fengtian

AU - Roman, Linda J.

AU - Silverman, Richard B.

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AB - A common dichotomy exists in inhibitor design: should the compounds be designed to block the enzymes of animals in the preclinical studies or to inhibit the human enzyme? We report that a single mutation of Leu-337 in rat neuronal nitric oxide synthase (nNOS) to His makes the enzyme resemble human nNOS more than rat nNOS. We expect that the approach used in this study can unite the dichotomy and speed up the process of inhibitor design and development.

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L337H mutant of rat neuronal nitric oxide synthase resembles human neuronal nitric oxide synthase toward inhibitors

Abstract

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