Structure and nucleotide specificity of Staphylococcus aureus dihydrodipicolinate reductase (DapB)

Girish, Tavarekere S and Navratna, Vikas and Gopal, B (2011) Structure and nucleotide specificity of Staphylococcus aureus dihydrodipicolinate reductase (DapB). In: FEBS Letters, 585 (16). pp. 2561-2567.

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Abstract

Lysine biosynthesis proceeds by the nucleotide-dependent reduction of dihydrodipicolinate (DHDP) to tetrahydrodipicolinate (THDP) by dihydrodipicolinate reductase (DHDPR). The S. aureus DHDPR structure reveals different conformational states of this enzyme even in the absence of a substrate or nucleotide-cofactor. Despite lacking a conserved basic residue essential for NADPH interaction, S. aureus DHDPR differs from other homologues as NADPH is a more preferred co-factor than NADH. The structure provides a rationale-Lys35 compensates for the co-factor site mutation. These observations are significant for bi-ligand inhibitor design that relies on ligand-induced conformational changes as well as co-factor specificity for this important drug target. Structured summary of protein interactions: DHDPR binds to DHDPR by molecular sieving (View interaction). DHDPR binds to DHDPR by dynamic light scattering (View interaction). DHDPR binds to DHDPR by X-ray crystallography (View interaction). (C) 2011 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.

Item Type:	Journal Article
Publication:	FEBS Letters
Publisher:	Elsevier Science B.V.
Additional Information:	Copyright of this article belongs to Elsevier Science B.V.
Keywords:	DHDPR;DapB;MRSA;Lysine/m-Dap biosynthesis
Department/Centre:	Division of Biological Sciences > Molecular Biophysics Unit
Date Deposited:	03 Sep 2011 10:24
Last Modified:	03 Sep 2011 10:24
URI:	http://eprints.iisc.ac.in/id/eprint/40407

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