Structure of HsaD, a steroid-degrading hydrolase, from Mycobacterium tuberculosis
- Department of Pharmacology, University of Oxford, Mansfield Road, Oxford OX1 3QT (United Kingdom)
- Laboratory of Molecular Biophysics, Department of Biochemistry, University of Oxford, South Parks Road, Oxford OX1 3QU (United Kingdom)
- Department of Microbiology and Immunology, Life Sciences Institute, University of British Columbia, Vancouver BC V6T 1Z3 (Canada)
The structure of HsaD, a carbon–carbon bond serine hydrolase involved in steroid catabolism that is critical for the survival of M. tuberculosis inside human macrophages, has been solved by X-ray crystallography. Data were collected at the Diamond Light Source in Oxfordshire, England: this paper describes one of the first structures determined at the new synchrotron. 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.
- OSTI ID:
- 22360463
- Journal Information:
- Acta Crystallographica. Section F, Journal Name: Acta Crystallographica. Section F Journal Issue: Pt 1 Vol. 64; ISSN ACSFCL; ISSN 1744-3091
- Country of Publication:
- United Kingdom
- Language:
- English
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