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Structure of HsaD, a steroid-degrading hydrolase, from Mycobacterium tuberculosis

DOI: 10.1107/S1744309107065931 DOI Help
PMID: 18097091 PMID Help

Authors: Nathan Lack (University of Oxford) , Edward D. Lowe (University of Oxford) , Jie Liu (University of British Columbia) , Lindsay D. Eltis (University of British Columbia) , Martin E. M. Noble (University of Oxford) , Edith Sim (University of Oxford) , Isaac M. Westwood (University of Oxford)
Co-authored by industrial partner: No

Type: Journal Paper
Journal: Acta Crystallographica Section F Structural Biology And Crystallization Communications , VOL 64 , PAGES 2 - 7

State: Published (Approved)
Published: January 2008

Open Access Open Access

Abstract: Tuberculosis is a major cause of death worldwide. Understanding of the pathogenicity of Mycobacterium tuberculosis has been advanced by gene analysis and has led to the identification of genes that are important for intracellular survival in macrophages. One of these genes encodes HsaD, a meta-cleavage product (MCP) hydrolase that catalyzes the hydrolytic cleavage of a carbon-carbon bond in cholesterol metabolism. This paper describes the production of HsaD as a recombinant protein and, following crystallization, the determination of its three-dimensional structure to 2.35 Å resolution by X-ray crystallography at the Diamond Light Source in Oxfordshire, England. To the authors' knowledge, this study constitutes the first report of a structure determined at the new synchrotron facility. The volume of the active-site cleft of the HsaD enzyme is more than double the corresponding active-site volumes of related MCP hydrolases involved in the catabolism of aromatic compounds, consistent with the specificity of HsaD for steroids such as cholesterol. Knowledge of the structure of the enzyme facilitates the design of inhibitors.

Journal Keywords: Bacterial; Cloning; Molecular; Conserved; Hydrolases; Models; Molecular; Mycobacterium; Protein; Recombinant; Sequence; Steroid Hydroxylases; Cholesterol; Cleavage; Crystallization; Crystallography; Design; Diamonds; Light Sources; Resolution; Specificity

Subject Areas: Biology and Bio-materials

Instruments: I04-Macromolecular Crystallography