uu.seUppsala University Publications
Change search
ReferencesLink to record
Permanent link

Direct link
Rv0216, a conserved hypothetical protein from Mycobacterium tuberculosis that is essential for bacterial
Uppsala University, Teknisk-naturvetenskapliga vetenskapsområdet, Faculty of Science and Technology, Biology, Department of Cell and Molecular Biology.
Show others and affiliations
Manuscript (Other academic)
URN: urn:nbn:se:uu:diva-97709OAI: oai:DiVA.org:uu-97709DiVA: diva2:172751
Available from: 2008-11-06 Created: 2008-11-06 Last updated: 2010-01-13Bibliographically approved
In thesis
1. Fighting Tuberculosis –: Structural Studies of Three Mycobacterial Proteins
Open this publication in new window or tab >>Fighting Tuberculosis –: Structural Studies of Three Mycobacterial Proteins
2008 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

This thesis presents the cloning, purification, crystallization, and structural studies of two unknown proteins from Mycobacterium tuberculosis, and of an aminotransferase from Mycobacterium smegmatis. Structural knowledge of these proteins is of highest interest for structure-based drug design, which is one of the approaches that can be used in order to fight tuberculosis (TB).

The structure of the conserved hypothetical protein Rv0216 was refined to a resolution of 1.9 Å. The structure exhibits a so-called double hotdog-fold, similar to known hydratases. However, only parts of the hydratase active site are conserved in Rv0216, and no function could be assigned to the protein. Several Rv0216-like protein sequences were found in a variety of actino- and proteobacteria, suggesting that these proteins form a new protein family. Furthermore, other hotdog-folded proteins in M. tuberculosis were identified, of which a few are likely to be hydratases or dehydratases involved in the fatty acid metabolism.

The structure of Rv0130 exhibits a single hotdog-fold and contains a highly conserved R-hydratase motif. Rv0130 was shown to hydrate fatty acid coenzyme A derivatives with a length of six to eight carbons. The Rv0130 active site is situated in a long tunnel, formed by a kink in the central hotdog-helix, which indicate that it can utilize long fatty acid chains as well. A number of previously predicted hotdog-folded proteins also feature a similar tunnel.

The structure of branched chain aminotransferase (BCAT) of M. smegmatis was determined in the apo-form and in complex with an aminooxy inhibitor. Mycobacterial BCAT is very similar to the human BCAT, apart for one important difference in the active site. Gly243 is a threonine in the human BCAT, a difference that offers specificity in inhibition and substrate recognition of these proteins. The aminooxy compound and MES were found to inhibit the mycobacterial BCAT activities. The aminooxy compound inhibits by blocking the substrate-pocket. A second inhibitor-binding site was identified through the binding of a MES molecule. Therefore, both the MES-binding site and the substrate-pocket of M. smegmatis BCAT are suggested to be potential sites for the development of new inhibitors against tuberculosis.

Place, publisher, year, edition, pages
Uppsala: Universitetsbiblioteket, 2008. 94 p.
Digital Comprehensive Summaries of Uppsala Dissertations from the Faculty of Science and Technology, ISSN 1651-6214 ; 567
Mycobacterium tuberculosis, Rv0216, Rv0130, Mycobacterium smegmatis, branched chain aminotransferase, X-ray crystallography, fatty acid metabolism
National Category
Structural Biology
urn:nbn:se:uu:diva-9348 (URN)978-91-554-7325-9 (ISBN)
Public defence
2008-11-29, B42, BMC, Husargatan 3, Uppsala, 13:15 (English)
Available from: 2008-11-06 Created: 2008-11-06 Last updated: 2011-06-10Bibliographically approved

Open Access in DiVA

No full text

By organisation
Department of Cell and Molecular Biology

Search outside of DiVA

GoogleGoogle Scholar
The number of downloads is the sum of all downloads of full texts. It may include eg previous versions that are now no longer available

Total: 200 hits
ReferencesLink to record
Permanent link

Direct link