5hm3
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==2.25 Angstrom Resolution Crystal Structure of Long-chain-fatty-acid-AMP Ligase FadD32 from Mycobacterium tuberculosis in complex with Inhibitor 5'-O-[(11-phenoxyundecanoyl)sulfamoyl]adenosine== | ==2.25 Angstrom Resolution Crystal Structure of Long-chain-fatty-acid-AMP Ligase FadD32 from Mycobacterium tuberculosis in complex with Inhibitor 5'-O-[(11-phenoxyundecanoyl)sulfamoyl]adenosine== | ||
| - | <StructureSection load='5hm3' size='340' side='right' caption='[[5hm3]], [[Resolution|resolution]] 2.25Å' scene=''> | + | <StructureSection load='5hm3' size='340' side='right'caption='[[5hm3]], [[Resolution|resolution]] 2.25Å' scene=''> |
== Structural highlights == | == Structural highlights == | ||
| - | <table><tr><td colspan='2'>[[5hm3]] is a 1 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5HM3 OCA]. For a <b>guided tour on the structure components</b> use [ | + | <table><tr><td colspan='2'>[[5hm3]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Mycobacterium_tuberculosis_H37Rv Mycobacterium tuberculosis H37Rv]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5HM3 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5HM3 FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=649:5-O-[(11-PHENOXYUNDECANOYL)SULFAMOYL]ADENOSINE'>649</scene>, <scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand= | + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.25Å</td></tr> |
| - | + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=649:5-O-[(11-PHENOXYUNDECANOYL)SULFAMOYL]ADENOSINE'>649</scene>, <scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=CME:S,S-(2-HYDROXYETHYL)THIOCYSTEINE'>CME</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=MSE:SELENOMETHIONINE'>MSE</scene>, <scene name='pdbligand=PEG:DI(HYDROXYETHYL)ETHER'>PEG</scene>, <scene name='pdbligand=PO4:PHOSPHATE+ION'>PO4</scene></td></tr> | |
| - | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[ | + | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=5hm3 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5hm3 OCA], [https://pdbe.org/5hm3 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5hm3 RCSB], [https://www.ebi.ac.uk/pdbsum/5hm3 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5hm3 ProSAT]</span></td></tr> |
</table> | </table> | ||
== Function == | == Function == | ||
| - | [ | + | [https://www.uniprot.org/uniprot/FAA32_MYCTU FAA32_MYCTU] Catalyzes the activation of long-chain fatty acids as acyl-adenylates (acyl-AMP), which are then transferred to the multifunctional polyketide synthase (PKS) for further chain extension.<ref>PMID:15042094</ref> |
| + | <div style="background-color:#fffaf0;"> | ||
| + | == Publication Abstract from PubMed == | ||
| + | Mycolic acids are indispensible lipids of Mycobacterium tuberculosis (Mtb), the causative agent of tuberculosis (TB), and contribute to the distinctive architecture and impermeability of the mycobacterial cell envelope. FadD32 plays a pivotal role in mycolic acid biosynthesis by functionally linking fatty acid synthase (FAS) and polyketide synthase (PKS) biosynthetic pathways. FadD32, a fatty acyl-AMP ligase (FAAL), represents one of the best genetically and chemically validated new TB drug targets. We have determined the three-dimensional crystal structure of Mtb FadD32 in complex with a ligand specifically designed to stabilize the catalytically active adenylate-conformation, which provides a foundation for structure-based drug design efforts against this essential protein. The structure also captures the unique interactions of a FAAL-specific insertion sequence and provides insight into the specificity and mechanism of fatty acid transfer. | ||
| + | |||
| + | Structure of the Essential Mtb FadD32 Enzyme: A Promising Drug Target for Treating Tuberculosis.,Kuhn ML, Alexander E, Minasov G, Page HJ, Warwrzak Z, Shuvalova L, Flores KJ, Wilson DJ, Shi C, Aldrich CC, Anderson WF ACS Infect Dis. 2016 Aug 12;2(8):579-591. Epub 2016 Jul 1. PMID:27547819<ref>PMID:27547819</ref> | ||
| + | |||
| + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | ||
| + | </div> | ||
| + | <div class="pdbe-citations 5hm3" style="background-color:#fffaf0;"></div> | ||
== References == | == References == | ||
<references/> | <references/> | ||
__TOC__ | __TOC__ | ||
</StructureSection> | </StructureSection> | ||
| - | [[Category: | + | [[Category: Large Structures]] |
| - | [[Category: | + | [[Category: Mycobacterium tuberculosis H37Rv]] |
| - | [[Category: | + | [[Category: Aldrich CC]] |
| - | [[Category: Flores | + | [[Category: Anderson WA]] |
| - | [[Category: Grimes | + | [[Category: Flores KJ]] |
| - | [[Category: Kuhn | + | [[Category: Grimes KD]] |
| - | [[Category: Minasov | + | [[Category: Kuhn ML]] |
| - | [[Category: Shuvalova | + | [[Category: Minasov G]] |
| - | [[Category: Warwrzak | + | [[Category: Shuvalova L]] |
| - | [[Category: Wilson | + | [[Category: Warwrzak Z]] |
| - | + | [[Category: Wilson DJ]] | |
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Current revision
2.25 Angstrom Resolution Crystal Structure of Long-chain-fatty-acid-AMP Ligase FadD32 from Mycobacterium tuberculosis in complex with Inhibitor 5'-O-[(11-phenoxyundecanoyl)sulfamoyl]adenosine
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