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| | <StructureSection load='1hzp' size='340' side='right'caption='[[1hzp]], [[Resolution|resolution]] 2.10Å' scene=''> | | <StructureSection load='1hzp' size='340' side='right'caption='[[1hzp]], [[Resolution|resolution]] 2.10Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[1hzp]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/"bacillus_tuberculosis"_(zopf_1883)_klein_1884 "bacillus tuberculosis" (zopf 1883) klein 1884]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1HZP OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1HZP FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[1hzp]] is a 2 chain structure with sequence from [https://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]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1HZP FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=DAO:LAURIC+ACID'>DAO</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene></td></tr> | + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.1Å</td></tr> |
| - | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat"><div style='overflow: auto; max-height: 3em;'>[[1ebl|1ebl]], [[1hnj|1hnj]]</div></td></tr> | + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=DAO:LAURIC+ACID'>DAO</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene></td></tr> |
| - | <tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[https://en.wikipedia.org/wiki/Beta-ketoacyl-[acyl-carrier-protein]_synthase_I Beta-ketoacyl-[acyl-carrier-protein] synthase I], with EC number [https://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.3.1.41 2.3.1.41] </span></td></tr>
| + | |
| | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=1hzp FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1hzp OCA], [https://pdbe.org/1hzp PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1hzp RCSB], [https://www.ebi.ac.uk/pdbsum/1hzp PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1hzp ProSAT]</span></td></tr> | | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=1hzp FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1hzp OCA], [https://pdbe.org/1hzp PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1hzp RCSB], [https://www.ebi.ac.uk/pdbsum/1hzp PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1hzp ProSAT]</span></td></tr> |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[https://www.uniprot.org/uniprot/FABH_MYCTU FABH_MYCTU]] Catalyzes the condensation reaction of fatty acid synthesis by the addition to an acyl acceptor of two carbons from malonyl-ACP. Catalyzes the first condensation reaction which initiates fatty acid synthesis and may therefore play a role in governing the total rate of fatty acid production. Possesses both acetoacetyl-ACP synthase and acetyl transacylase activities. Has some substrate specificity for long chain acyl-CoA such as myristoyl-CoA. Does not use acyl-CoA as primer. Its substrate specificity determines the biosynthesis of mycolic acid fatty acid chain, which is characteristic of mycobacterial cell wall.<ref>PMID:10840036</ref>
| + | [https://www.uniprot.org/uniprot/FABH_MYCTU FABH_MYCTU] Catalyzes the condensation reaction of fatty acid synthesis by the addition to an acyl acceptor of two carbons from malonyl-ACP. Catalyzes the first condensation reaction which initiates fatty acid synthesis and may therefore play a role in governing the total rate of fatty acid production. Possesses both acetoacetyl-ACP synthase and acetyl transacylase activities. Has some substrate specificity for long chain acyl-CoA such as myristoyl-CoA. Does not use acyl-CoA as primer. Its substrate specificity determines the biosynthesis of mycolic acid fatty acid chain, which is characteristic of mycobacterial cell wall.<ref>PMID:10840036</ref> |
| | == Evolutionary Conservation == | | == Evolutionary Conservation == |
| | [[Image:Consurf_key_small.gif|200px|right]] | | [[Image:Consurf_key_small.gif|200px|right]] |
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| | </StructureSection> | | </StructureSection> |
| | [[Category: Large Structures]] | | [[Category: Large Structures]] |
| - | [[Category: He, X]] | + | [[Category: Mycobacterium tuberculosis]] |
| - | [[Category: Kazanina, G]] | + | [[Category: He X]] |
| - | [[Category: Reynolds, K A]] | + | [[Category: Kazanina G]] |
| - | [[Category: Scarsdale, J N]] | + | [[Category: Reynolds KA]] |
| - | [[Category: Structural genomic]] | + | [[Category: Scarsdale JN]] |
| - | [[Category: Wright, H T]] | + | [[Category: Wright HT]] |
| - | [[Category: Fatty acid biosynthesis]]
| + | |
| - | [[Category: Myobacterium tuberculosis]]
| + | |
| - | [[Category: PSI, Protein structure initiative]]
| + | |
| - | [[Category: Structural basis for substrate specificity]]
| + | |
| - | [[Category: Tbsgc]]
| + | |
| - | [[Category: Transferase]]
| + | |
| Structural highlights
Function
FABH_MYCTU Catalyzes the condensation reaction of fatty acid synthesis by the addition to an acyl acceptor of two carbons from malonyl-ACP. Catalyzes the first condensation reaction which initiates fatty acid synthesis and may therefore play a role in governing the total rate of fatty acid production. Possesses both acetoacetyl-ACP synthase and acetyl transacylase activities. Has some substrate specificity for long chain acyl-CoA such as myristoyl-CoA. Does not use acyl-CoA as primer. Its substrate specificity determines the biosynthesis of mycolic acid fatty acid chain, which is characteristic of mycobacterial cell wall.[1]
Evolutionary Conservation
Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.
Publication Abstract from PubMed
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.
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[2]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Choi KH, Kremer L, Besra GS, Rock CO. Identification and substrate specificity of beta -ketoacyl (acyl carrier protein) synthase III (mtFabH) from Mycobacterium tuberculosis. J Biol Chem. 2000 Sep 8;275(36):28201-7. PMID:10840036 doi:http://dx.doi.org/10.1074/jbc.M003241200
- ↑ Scarsdale JN, Kazanina G, He X, Reynolds KA, Wright HT. Crystal structure of the Mycobacterium tuberculosis beta-ketoacyl-acyl carrier protein synthase III. J Biol Chem. 2001 Jun 8;276(23):20516-22. Epub 2001 Mar 8. PMID:11278743 doi:10.1074/jbc.M010762200
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