1F61

CRYSTAL STRUCTURE OF ISOCITRATE LYASE FROM MYCOBACTERIUM TUBERCULOSIS

Summary for 1F61

• Entry DOI: 10.2210/pdb1f61/pdb
• Descriptor: ISOCITRATE LYASE, MAGNESIUM ION (3 entities in total)
• Functional Keywords: alpha-beta barrel, swapped helices, apo-enzyme, open conformation, structural genomics, psi, protein structure initiative, tb structural genomics consortium, tbsgc, lyase
• Biological source: Mycobacterium tuberculosis H37Rv
• Cellular location: Cytoplasm: P0A5H3
• Total number of polymer chains: 2
• Total formula weight: 94459.56

Authors

Sharma, V.,Sharma, S.,Hoener zu Bentrup, K.H.,McKinney, J.D.,Russell, D.G.,Jacobs Jr., W.R.,Sacchettini, J.C.,TB Structural Genomics Consortium (TBSGC) (deposition date: 2000-06-19, release date: 2000-08-30, Last modification date: 2024-02-07)

Primary citation

Sharma, V.,Sharma, S.,Hoener zu Bentrup, K.,McKinney, J.D.,Russell, D.G.,Jacobs Jr., W.R.,Sacchettini, J.C.
Structure of isocitrate lyase, a persistence factor of Mycobacterium tuberculosis.
Nat.Struct.Biol., 7:663-668, 2000

PubMed Abstract: 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: 10932251
DOI: 10.1038/77964

Experimental method

X-RAY DIFFRACTION (2 Å)