1hzp: Difference between revisions
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[[Image:1hzp.gif|left|200px]] | [[Image:1hzp.gif|left|200px]] | ||
'''Crystal Structure of the Myobacterium Tuberculosis Beta-Ketoacyl-Acyl Carrier Protein Synthase III''' | {{Structure | ||
|PDB= 1hzp |SIZE=350|CAPTION= <scene name='initialview01'>1hzp</scene>, resolution 2.10Å | |||
|SITE= | |||
|LIGAND= <scene name='pdbligand=DAO:LAURIC+ACID'>DAO</scene> and <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene> | |||
|ACTIVITY= [http://en.wikipedia.org/wiki/Beta-ketoacyl-acyl-carrier-protein_synthase_I Beta-ketoacyl-acyl-carrier-protein synthase I], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.3.1.41 2.3.1.41] | |||
|GENE= | |||
}} | |||
'''Crystal Structure of the Myobacterium Tuberculosis Beta-Ketoacyl-Acyl Carrier Protein Synthase III''' | |||
==Overview== | ==Overview== | ||
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==About this Structure== | ==About this Structure== | ||
1HZP is a [ | 1HZP is a [[Single protein]] structure of sequence from [http://en.wikipedia.org/wiki/Mycobacterium_tuberculosis Mycobacterium tuberculosis]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1HZP OCA]. | ||
==Reference== | ==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:[http:// | 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:[http://www.ncbi.nlm.nih.gov/pubmed/11278743 11278743] | ||
[[Category: Beta-ketoacyl-acyl-carrier-protein synthase I]] | [[Category: Beta-ketoacyl-acyl-carrier-protein synthase I]] | ||
[[Category: Mycobacterium tuberculosis]] | [[Category: Mycobacterium tuberculosis]] | ||
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[[Category: psi]] | [[Category: psi]] | ||
[[Category: structural basis for substrate specificity]] | [[Category: structural basis for substrate specificity]] | ||
[[Category: structural | [[Category: structural genomic]] | ||
[[Category: tb structural genomics consortium]] | [[Category: tb structural genomics consortium]] | ||
[[Category: tbsgc]] | [[Category: tbsgc]] | ||
''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Mar 20 11:43:38 2008'' | ||
Revision as of 12:43, 20 March 2008
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| , resolution 2.10Å | |||||||
|---|---|---|---|---|---|---|---|
| Ligands: | and | ||||||
| Activity: | Beta-ketoacyl-acyl-carrier-protein synthase I, with EC number 2.3.1.41 | ||||||
| Coordinates: | save as pdb, mmCIF, xml | ||||||
Crystal Structure of the Myobacterium Tuberculosis Beta-Ketoacyl-Acyl Carrier Protein Synthase III
OverviewOverview
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 StructureAbout this Structure
1HZP is a Single protein structure of sequence from Mycobacterium tuberculosis. Full crystallographic information is available from OCA.
ReferenceReference
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 Thu Mar 20 11:43:38 2008
Proteopedia Page Contributors and Editors (what is this?)Proteopedia Page Contributors and Editors (what is this?)
OCA- Pages with broken file links
- 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.
- DAO
- GOL
- Fatty acid biosynthesis
- Myobacterium tuberculosis
- Protein structure initiative
- Psi
- Structural basis for substrate specificity
- Structural genomic
- Tb structural genomics consortium
- Tbsgc