|
rdf:type |
|
|
lifeskim:mentions |
|
|
pubmed:issue |
8
|
|
pubmed:dateCreated |
2000-8-24
|
|
pubmed:databankReference |
|
|
pubmed:abstractText |
Isocitrate lyase (ICL) plays a pivotal role in the persistence of Mycobacterium tuberculosis in mice by sustaining intracellular infection in inflammatory macrophages. The enzyme allows net carbon gain by diverting acetyl-CoA from beta-oxidation of fatty acids into the glyoxylate shunt pathway. Given its potential as a drug target against persistent infections, we solved its structure without ligand and in complex with two inhibitors. Covalent modification of an active site residue, Cys 191, by the inhibitor 3-bromopyruvate traps the enzyme in a catalytic conformation with the active site completely inaccessible to solvent. The structure of a C191S mutant of the enzyme with the inhibitor 3-nitropropionate provides further insight into the reaction mechanism.
|
|
pubmed:language |
eng
|
|
pubmed:journal |
|
|
pubmed:citationSubset |
IM
|
|
pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/3-nitropropionic acid,
http://linkedlifedata.com/resource/pubmed/chemical/Cysteine,
http://linkedlifedata.com/resource/pubmed/chemical/Glyoxylates,
http://linkedlifedata.com/resource/pubmed/chemical/Isocitrate Lyase,
http://linkedlifedata.com/resource/pubmed/chemical/Ligands,
http://linkedlifedata.com/resource/pubmed/chemical/Nitro Compounds,
http://linkedlifedata.com/resource/pubmed/chemical/Propionic Acids,
http://linkedlifedata.com/resource/pubmed/chemical/Pyruvates,
http://linkedlifedata.com/resource/pubmed/chemical/Solvents,
http://linkedlifedata.com/resource/pubmed/chemical/bromopyruvate,
http://linkedlifedata.com/resource/pubmed/chemical/glyoxylic acid
|
|
pubmed:status |
MEDLINE
|
|
pubmed:month |
Aug
|
|
pubmed:issn |
1072-8368
|
|
pubmed:author |
|
|
pubmed:issnType |
Print
|
|
pubmed:volume |
7
|
|
pubmed:owner |
NLM
|
|
pubmed:authorsComplete |
Y
|
|
pubmed:pagination |
663-8
|
|
pubmed:dateRevised |
2006-11-15
|
|
pubmed:meshHeading |
pubmed-meshheading:10932251-Amino Acid Substitution,
pubmed-meshheading:10932251-Animals,
pubmed-meshheading:10932251-Binding Sites,
pubmed-meshheading:10932251-Catalysis,
pubmed-meshheading:10932251-Crystallography, X-Ray,
pubmed-meshheading:10932251-Cysteine,
pubmed-meshheading:10932251-Glyoxylates,
pubmed-meshheading:10932251-Isocitrate Lyase,
pubmed-meshheading:10932251-Ligands,
pubmed-meshheading:10932251-Mice,
pubmed-meshheading:10932251-Models, Molecular,
pubmed-meshheading:10932251-Molecular Sequence Data,
pubmed-meshheading:10932251-Mutation,
pubmed-meshheading:10932251-Mycobacterium tuberculosis,
pubmed-meshheading:10932251-Nitro Compounds,
pubmed-meshheading:10932251-Propionic Acids,
pubmed-meshheading:10932251-Protein Binding,
pubmed-meshheading:10932251-Protein Structure, Secondary,
pubmed-meshheading:10932251-Protein Structure, Tertiary,
pubmed-meshheading:10932251-Pyruvates,
pubmed-meshheading:10932251-Solvents
|
|
pubmed:year |
2000
|
|
pubmed:articleTitle |
Structure of isocitrate lyase, a persistence factor of Mycobacterium tuberculosis.
|
|
pubmed:affiliation |
Department of Biochemistry and Biophysics, Texas A&M University, College Station, Texas 77843-2128, USA.
|
|
pubmed:publicationType |
Journal Article,
Research Support, U.S. Gov't, P.H.S.,
Research Support, U.S. Gov't, Non-P.H.S.,
Research Support, Non-U.S. Gov't
|
