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| | ==Crystal structure of N-terminal domain of FAAL28 G330W mutant from Mycobacterium tuberculosis== | | ==Crystal structure of N-terminal domain of FAAL28 G330W mutant from Mycobacterium tuberculosis== |
| - | <StructureSection load='3t5a' size='340' side='right' caption='[[3t5a]], [[Resolution|resolution]] 2.05Å' scene=''> | + | <StructureSection load='3t5a' size='340' side='right'caption='[[3t5a]], [[Resolution|resolution]] 2.05Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[3t5a]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Myctu Myctu]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3T5A OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3T5A FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[3t5a]] 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=3T5A OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3T5A FirstGlance]. <br> |
| - | </td></tr><tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[3e53|3e53]], [[3t5b|3t5b]], [[3t5c|3t5c]]</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]] 2.05Å</td></tr> |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">acoas, fadD28, MT3011, Rv2941 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=83332 MYCTU])</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=3t5a FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3t5a OCA], [https://pdbe.org/3t5a PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3t5a RCSB], [https://www.ebi.ac.uk/pdbsum/3t5a PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3t5a ProSAT]</span></td></tr> |
| - | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3t5a FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3t5a OCA], [http://pdbe.org/3t5a PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=3t5a RCSB], [http://www.ebi.ac.uk/pdbsum/3t5a PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=3t5a ProSAT]</span></td></tr> | + | |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/FAA28_MYCTU FAA28_MYCTU]] Catalyzes the activation of long-chain fatty acids (C22-24 fatty acids) as acyl-adenylates (acyl-AMP), which are then transferred to the multifunctional polyketide synthase Mas for further chain extension. Involved in the biosynthesis of mycoserates.<ref>PMID:10573420</ref> <ref>PMID:11279114</ref> <ref>PMID:15042094</ref> | + | [https://www.uniprot.org/uniprot/FAA28_MYCTU FAA28_MYCTU] Catalyzes the activation of long-chain fatty acids (C22-24 fatty acids) as acyl-adenylates (acyl-AMP), which are then transferred to the multifunctional polyketide synthase Mas for further chain extension. Involved in the biosynthesis of mycoserates.<ref>PMID:10573420</ref> <ref>PMID:11279114</ref> <ref>PMID:15042094</ref> |
| | <div style="background-color:#fffaf0;"> | | <div style="background-color:#fffaf0;"> |
| | == Publication Abstract from PubMed == | | == Publication Abstract from PubMed == |
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| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Myctu]] | + | [[Category: Large Structures]] |
| - | [[Category: Goyal, A]] | + | [[Category: Mycobacterium tuberculosis H37Rv]] |
| - | [[Category: Sankaranarayanan, R]] | + | [[Category: Goyal A]] |
| - | [[Category: Acetyl-coa synthetase like fold]] | + | [[Category: Sankaranarayanan R]] |
| - | [[Category: Amp-binding]]
| + | |
| - | [[Category: Ligase]]
| + | |
| Structural highlights
Function
FAA28_MYCTU Catalyzes the activation of long-chain fatty acids (C22-24 fatty acids) as acyl-adenylates (acyl-AMP), which are then transferred to the multifunctional polyketide synthase Mas for further chain extension. Involved in the biosynthesis of mycoserates.[1] [2] [3]
Publication Abstract from PubMed
Activation of fatty acids as acyl-adenylates by fatty acyl-AMP ligases (FAALs) in Mycobacterium tuberculosis is a variant of a classical theme that involves formation of acyl-CoA (coenzyme A) by fatty acyl-CoA ligases (FACLs). Here, we show that FAALs and FACLs possess similar structural fold and substrate specificity determinants, and the key difference is the absence of a unique insertion sequence in FACL13 structure. A systematic analysis shows a conserved hydrophobic anchorage of the insertion motif across several FAALs. Strikingly, mutagenesis of two phenylalanine residues, which are part of the anchorage, to alanine converts FAAL32 to FACL32. This insertion-based in silico analysis suggests the presence of FAAL homologues in several other non-mycobacterial genomes including eukaryotes. The work presented here establishes an elegant mechanism wherein an insertion sequence drives the functional divergence of FAALs from canonical FACLs.
Molecular Basis of the Functional Divergence of Fatty Acyl-AMP Ligase Biosynthetic Enzymes of Mycobacterium tuberculosis.,Goyal A, Verma P, Anandhakrishnan M, Gokhale RS, Sankaranarayanan R J Mol Biol. 2011 Dec 21. PMID:22206988[4]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Cox JS, Chen B, McNeil M, Jacobs WR Jr. Complex lipid determines tissue-specific replication of Mycobacterium tuberculosis in mice. Nature. 1999 Nov 4;402(6757):79-83. PMID:10573420 doi:10.1038/47042
- ↑ Camacho LR, Constant P, Raynaud C, Laneelle MA, Triccas JA, Gicquel B, Daffe M, Guilhot C. Analysis of the phthiocerol dimycocerosate locus of Mycobacterium tuberculosis. Evidence that this lipid is involved in the cell wall permeability barrier. J Biol Chem. 2001 Jun 8;276(23):19845-54. Epub 2001 Mar 13. PMID:11279114 doi:10.1074/jbc.M100662200
- ↑ Trivedi OA, Arora P, Sridharan V, Tickoo R, Mohanty D, Gokhale RS. Enzymic activation and transfer of fatty acids as acyl-adenylates in mycobacteria. Nature. 2004 Mar 25;428(6981):441-5. PMID:15042094 doi:10.1038/nature02384
- ↑ Goyal A, Verma P, Anandhakrishnan M, Gokhale RS, Sankaranarayanan R. Molecular Basis of the Functional Divergence of Fatty Acyl-AMP Ligase Biosynthetic Enzymes of Mycobacterium tuberculosis. J Mol Biol. 2011 Dec 21. PMID:22206988 doi:10.1016/j.jmb.2011.12.031
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