2QNZ
Crystal structure of the complex between the mycobacterium beta-ketoacyl-acyl carrier protein synthase III (FABH) and SS-(2-hydroxyethyl)-O-decyl ester carbono(dithioperoxoic) acid
Summary for 2QNZ
| Entry DOI | 10.2210/pdb2qnz/pdb |
| Related | 1HNJ 1HNK 1HZP 1U6E 1U6S 2QNX 2QNY 2QO0 2QO1 |
| Descriptor | 3-oxoacyl-[acyl-carrier-protein] synthase 3, DECYL FORMATE, BETA-MERCAPTOETHANOL, ... (4 entities in total) |
| Functional Keywords | fatty acid biosynthesis, myobacterium tuberculosis, structural basis for substrate specificity, enzyme inhibitor complex, mechanism based inhibitor, acyltransferase, cytoplasm, lipid synthesis, multifunctional enzyme, transferase |
| Biological source | Mycobacterium tuberculosis |
| Cellular location | Cytoplasm: P0A574 |
| Total number of polymer chains | 2 |
| Total formula weight | 70335.63 |
| Authors | Sachdeva, S.,Musayev, F.,Alhamadsheh, M.,Scarsdale, J.N.,Wright, H.T.,Reynolds, K.A. (deposition date: 2007-07-19, release date: 2008-05-06, Last modification date: 2023-08-30) |
| Primary citation | Sachdeva, S.,Musayev, F.N.,Alhamadsheh, M.M.,Scarsdale, J.N.,Wright, H.T.,Reynolds, K.A. Separate Entrance and Exit Portals for Ligand Traffic in Mycobacterium tuberculosis FabH Chem.Biol., 15:402-412, 2008 Cited by PubMed Abstract: Mycobacterium tuberculosis FabH initiates type II fatty acid synthase-catalyzed formation of the long chain (C(16)-C(22)) acyl-coenzyme A (CoA) precursors of mycolic acids, which are major constituents of the bacterial cell envelope. Crystal structures of M. tuberculosis FabH (mtFabH) show the substrate binding site to be a buried, extended L-shaped channel with only a single solvent access portal. Entrance of an acyl-CoA substrate through the solvent portal would require energetically unfavorable reptational threading of the substrate to its reactive position. Using a class of FabH inhibitors, we have tested an alternative hypothesis that FabH exists in an "open" form during substrate binding and product release, and a "closed" form in which catalysis and intermediate steps occur. This hypothesis is supported by mass spectrometric analysis of the product profile and crystal structures of complexes of mtFabH with these inhibitors. PubMed: 18420147DOI: 10.1016/j.chembiol.2008.03.007 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (2.3 Å) |
Structure validation
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