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

Direct link
Cite
Citation style
  • apa
  • ieee
  • modern-language-association
  • vancouver
  • Other style
More styles
Language
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Other locale
More languages
Output format
  • html
  • text
  • asciidoc
  • rtf
Structure and function of carbonic anhydrases from Mycobacterium tuberculosis
Uppsala University, Teknisk-naturvetenskapliga vetenskapsområdet, Faculty of Science and Technology, Biology, Department of Cell and Molecular Biology.
Show others and affiliations
2005 In: J. Biol. Chem, Vol. 280, 18782-89 p.Article in journal (Refereed) Published
Place, publisher, year, edition, pages
2005. Vol. 280, 18782-89 p.
Identifiers
URN: urn:nbn:se:uu:diva-96917OAI: oai:DiVA.org:uu-96917DiVA: diva2:171653
Available from: 2008-03-20 Created: 2008-03-20Bibliographically approved
In thesis
1. Targeting Mycobacterium tuberculosis Proteins: Structure and Function Studies of Five Essential Proteins
Open this publication in new window or tab >>Targeting Mycobacterium tuberculosis Proteins: Structure and Function Studies of Five Essential Proteins
2008 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

This thesis describes the target selection, cloning, expression, purification, crystallization, structure and biochemical characterization of five essential Mycobacterium tuberculosis (Mtb) proteins. The search for drugs against the causal agent of tuberculosis is urgently needed and the targeting of essential genes is necessary to fulfill this goal.

The crystal structures of carbonic anhydrases (CA) Rv1284 and Rv3588c have been determined to 2.0 and 1.7 Å resolution, respectively. Rv3588c, in contrast to Rv1284, is an active β-CA that shows two different active site conformations and pH-dependent oligomerization states.

Rv1295 is an active threonine synthase with an unusually high pH optimum; the structure has been solved to 2.5 Å resolution, based on which a modification to the reaction mechanism published previously is proposed.

Mtb has a thick and impermeable cell envelope that constitutes an efficient barrier against drugs. One of the essential components of the envelope is mycolic acid (MA). The inhibition of enzymes participating in its synthesis would be lethal for Mtb. Rv0636, a formerly unknown-function protein has β-hydroxyacyl-ACP dehydrase activity which is essential for MA synthesis. Co-expression with partners notably improves its solubility.

Around 55% of Mtb proteins have unknown function. Rv3778c is one of them and its three-dimensional structure has been determined to 1.8 Å resolution. Studies aimed at the elucidation of its biochemical function are shown. A pathway not yet reported in Mtb is also suggested.

Place, publisher, year, edition, pages
Uppsala: Acta Universitatis Upsaliensis, 2008. 61 p.
Series
Digital Comprehensive Summaries of Uppsala Dissertations from the Faculty of Science and Technology, ISSN 1651-6214 ; 411
Keyword
Cell and molecular biology, carbonic anhydrase, threonine synthase, FAS II, Rv0636, Rv1284, Rv1295, Rv3588c, Rv3778c, X-ray crystallography, Cell- och molekylärbiologi, Mycobacterium tuberculosis
Identifiers
urn:nbn:se:uu:diva-8580 (URN)978-91-554-7134-7 (ISBN)
Public defence
2008-04-11, B42, BMC, Husargatan 3, Uppsala, 13:00 (English)
Opponent
Supervisors
Available from: 2008-03-20 Created: 2008-03-20 Last updated: 2009-06-01Bibliographically approved

Open Access in DiVA

No full text

By organisation
Department of Cell and Molecular Biology

Search outside of DiVA

GoogleGoogle Scholar

urn-nbn

Altmetric score

urn-nbn
Total: 475 hits
CiteExportLink to record
Permanent link

Direct link
Cite
Citation style
  • apa
  • ieee
  • modern-language-association
  • vancouver
  • Other style
More styles
Language
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Other locale
More languages
Output format
  • html
  • text
  • asciidoc
  • rtf