Abstract
L-Histidinol dehydrogenase from Brucella suis (BsHDH) is an enzyme involved in the histidine biosynthesis pathway which is absent in mammals, thus representing a very interesting target for the development of anti-Brucella agents. In this paper we report the crystallographic structure of a mutated form of BsHDH both in its unbound form and in complex with a nanomolar inhibitor. These studies provide the first structural background for the rational design of potent HDH inhibitors, thus offering new hints for clinical applications.
Keywords:
Brucella suis; Drug design; Inhibitor; X-ray crystallography; l-Histidinol dehydrogenase.
Copyright © 2013 Elsevier Masson SAS. All rights reserved.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Alcohol Oxidoreductases / antagonists & inhibitors
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Alcohol Oxidoreductases / chemistry*
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Alcohol Oxidoreductases / genetics
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Amino Acid Sequence
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Anti-Bacterial Agents / chemistry*
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Bacterial Proteins / antagonists & inhibitors
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Bacterial Proteins / chemistry*
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Bacterial Proteins / genetics
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Brucella suis / chemistry*
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Brucella suis / enzymology
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Butanones / chemistry*
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Catalytic Domain
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Crystallography, X-Ray
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Drug Design
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Enzyme Inhibitors / chemistry*
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Escherichia coli / enzymology
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Escherichia coli / genetics
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Gene Expression
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Histidine / chemistry
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Histidine / metabolism
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Imidazoles / chemistry*
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Molecular Docking Simulation
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Molecular Sequence Data
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Mutation
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Protein Structure, Quaternary
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Protein Structure, Secondary
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Protein Structure, Tertiary
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Recombinant Proteins / chemistry
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Recombinant Proteins / genetics
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Sequence Alignment
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Sequence Homology, Amino Acid
Substances
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3-amino-4-(1H-imidazol-5-yl)-1-(4-(phenylmethoxy)phenyl)butan-2-one
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Anti-Bacterial Agents
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Bacterial Proteins
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Butanones
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Enzyme Inhibitors
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Imidazoles
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Recombinant Proteins
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Histidine
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Alcohol Oxidoreductases
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histidinol dehydrogenase