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Structure and function of GlmU from Mycobacterium tuberculosis.
- Source :
-
Acta crystallographica. Section D, Biological crystallography [Acta Crystallogr D Biol Crystallogr] 2009 Mar; Vol. 65 (Pt 3), pp. 275-83. Date of Electronic Publication: 2009 Feb 20. - Publication Year :
- 2009
-
Abstract
- Antibiotic resistance is a major issue in the treatment of infectious diseases such as tuberculosis. Existing antibiotics target only a few cellular pathways and there is an urgent need for antibiotics that have novel molecular mechanisms. The glmU gene is essential in Mycobacterium tuberculosis, being required for optimal bacterial growth, and has been selected as a possible drug target for structural and functional investigation. GlmU is a bifunctional acetyltransferase/uridyltransferase that catalyses the formation of UDP-GlcNAc from GlcN-1-P. UDP-GlcNAc is a substrate for two important biosynthetic pathways: lipopolysaccharide and peptidoglycan synthesis. The crystal structure of M. tuberculosis GlmU has been determined in an unliganded form and in complex with GlcNAc-1-P or UDP-GlcNAc. The structures reveal the residues that are responsible for substrate binding. Enzyme activities were characterized by (1)H NMR and suggest that the presence of acetyl-coenzyme A has an inhibitory effect on uridyltransferase activity.
- Subjects :
- Acetylglucosamine analogs & derivatives
Acetylglucosamine metabolism
Acetyltransferases physiology
Bacterial Proteins physiology
Crystallography, X-Ray
Ligands
Magnesium metabolism
Models, Molecular
Multienzyme Complexes physiology
Nucleotidyltransferases physiology
Protein Conformation
Protein Structure, Tertiary
Structure-Activity Relationship
Uridine Diphosphate N-Acetylglucosamine metabolism
Acetyltransferases chemistry
Bacterial Proteins chemistry
Multienzyme Complexes chemistry
Mycobacterium tuberculosis enzymology
Nuclear Magnetic Resonance, Biomolecular
Nucleotidyltransferases chemistry
Subjects
Details
- Language :
- English
- ISSN :
- 1399-0047
- Volume :
- 65
- Issue :
- Pt 3
- Database :
- MEDLINE
- Journal :
- Acta crystallographica. Section D, Biological crystallography
- Publication Type :
- Academic Journal
- Accession number :
- 19237750
- Full Text :
- https://doi.org/10.1107/S0907444909001036