1hzp
From Proteopedia
| Line 1: | Line 1: | ||
[[Image:1hzp.gif|left|200px]] | [[Image:1hzp.gif|left|200px]] | ||
| - | + | <!-- | |
| - | + | The line below this paragraph, containing "STRUCTURE_1hzp", creates the "Structure Box" on the page. | |
| - | + | You may change the PDB parameter (which sets the PDB file loaded into the applet) | |
| - | + | or the SCENE parameter (which sets the initial scene displayed when the page is loaded), | |
| - | + | or leave the SCENE parameter empty for the default display. | |
| - | | | + | --> |
| - | | | + | {{STRUCTURE_1hzp| PDB=1hzp | SCENE= }} |
| - | + | ||
| - | + | ||
| - | }} | + | |
'''Crystal Structure of the Myobacterium Tuberculosis Beta-Ketoacyl-Acyl Carrier Protein Synthase III''' | '''Crystal Structure of the Myobacterium Tuberculosis Beta-Ketoacyl-Acyl Carrier Protein Synthase III''' | ||
| Line 32: | Line 29: | ||
[[Category: TBSGC, TB Structural Genomics Consortium.]] | [[Category: TBSGC, TB Structural Genomics Consortium.]] | ||
[[Category: Wright, H T.]] | [[Category: Wright, H T.]] | ||
| - | [[Category: | + | [[Category: Fatty acid biosynthesis]] |
| - | [[Category: | + | [[Category: Myobacterium tuberculosis]] |
| - | [[Category: | + | [[Category: Protein structure initiative]] |
| - | [[Category: | + | [[Category: Psi]] |
| - | [[Category: | + | [[Category: Structural basis for substrate specificity]] |
| - | [[Category: | + | [[Category: Structural genomic]] |
| - | [[Category: | + | [[Category: Tb structural genomics consortium]] |
| - | [[Category: | + | [[Category: Tbsgc]] |
| - | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Fri May 2 19:24:21 2008'' | |
| - | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on | + | |
Revision as of 16:24, 2 May 2008
Crystal Structure of the Myobacterium Tuberculosis Beta-Ketoacyl-Acyl Carrier Protein Synthase III
Overview
Mycolic acids (alpha-alkyl-beta-hydroxy long chain fatty acids) cover the surface of mycobacteria, and inhibition of their biosynthesis is an established mechanism of action for several key front-line anti-tuberculosis drugs. In mycobacteria, long chain acyl-CoA products (C(14)-C(26)) generated by a type I fatty-acid synthase can be used directly for the alpha-branch of mycolic acid or can be extended by a type II fatty-acid synthase to make the meromycolic acid (C(50)-C(56)))-derived component. An unusual Mycobacterium tuberculosis beta-ketoacyl-acyl carrier protein (ACP) synthase III (mtFabH) has been identified, purified, and shown to catalyze a Claisen-type condensation between long chain acyl-CoA substrates such as myristoyl-CoA (C(14)) and malonyl-ACP. This enzyme, presumed to play a key role in initiating meromycolic acid biosynthesis, was crystallized, and its structure was determined at 2.1-A resolution. The mtFabH homodimer is closely similar in topology and active-site structure to Escherichia coli FabH (ecFabH), with a CoA/malonyl-ACP-binding channel leading from the enzyme surface to the buried active-site cysteine residue. Unlike ecFabH, mtFabH contains a second hydrophobic channel leading from the active site. In the ecFabH structure, this channel is blocked by a phenylalanine residue, which constrains specificity to acetyl-CoA, whereas in mtFabH, this residue is a threonine, which permits binding of longer acyl chains. This same channel in mtFabH is capped by an alpha-helix formed adjacent to a 4-amino acid sequence insertion, which limits bound acyl chain length to 16 carbons. These observations offer a molecular basis for understanding the unusual substrate specificity of mtFabH and its probable role in regulating the biosynthesis of the two different length acyl chains required for generation of mycolic acids. This mtFabH presents a new target for structure-based design of novel antimycobacterial agents.
About this Structure
1HZP is a Single protein structure of sequence from Mycobacterium tuberculosis. Full crystallographic information is available from OCA.
Reference
Crystal structure of the Mycobacterium tuberculosis beta-ketoacyl-acyl carrier protein synthase III., Scarsdale JN, Kazanina G, He X, Reynolds KA, Wright HT, J Biol Chem. 2001 Jun 8;276(23):20516-22. Epub 2001 Mar 8. PMID:11278743 Page seeded by OCA on Fri May 2 19:24:21 2008
Categories: Beta-ketoacyl-acyl-carrier-protein synthase I | Mycobacterium tuberculosis | Single protein | He, X. | Kazanina, G. | Reynolds, K A. | Scarsdale, J N. | TBSGC, TB Structural Genomics Consortium. | Wright, H T. | Fatty acid biosynthesis | Myobacterium tuberculosis | Protein structure initiative | Psi | Structural basis for substrate specificity | Structural genomic | Tb structural genomics consortium | Tbsgc
