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| | ==Crystal Structure of phosphatidylinositol mannosyltransferase (PimA) from Mycobacterium smegmatis in complex with GDP-Man== | | ==Crystal Structure of phosphatidylinositol mannosyltransferase (PimA) from Mycobacterium smegmatis in complex with GDP-Man== |
| - | <StructureSection load='2gej' size='340' side='right' caption='[[2gej]], [[Resolution|resolution]] 2.60Å' scene=''> | + | <StructureSection load='2gej' size='340' side='right'caption='[[2gej]], [[Resolution|resolution]] 2.60Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[2gej]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Mycs2 Mycs2]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2GEJ OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2GEJ FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[2gej]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Mycs2 Mycs2]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2GEJ OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2GEJ FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=GDD:GUANOSINE-5-DIPHOSPHATE-ALPHA-D-MANNOSE'>GDD</scene></td></tr> | + | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=GDD:GUANOSINE-5-DIPHOSPHATE-ALPHA-D-MANNOSE'>GDD</scene></td></tr> |
| - | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[2gek|2gek]]</td></tr> | + | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat"><div style='overflow: auto; max-height: 3em;'>[[2gek|2gek]]</div></td></tr> |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">PIMA ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=246196 MYCS2])</td></tr> | + | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">PIMA ([https://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=246196 MYCS2])</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=2gej FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2gej OCA], [http://pdbe.org/2gej PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=2gej RCSB], [http://www.ebi.ac.uk/pdbsum/2gej PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=2gej 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=2gej FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2gej OCA], [https://pdbe.org/2gej PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2gej RCSB], [https://www.ebi.ac.uk/pdbsum/2gej PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2gej ProSAT]</span></td></tr> |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/PIMA_MYCS2 PIMA_MYCS2]] Catalyzes the addition of a mannose residue from GDP-D-mannose to the position 2 of a phosphatidyl-myo-inositol (PI) to generate a phosphatidyl-myo-inositol bearing an alpha-1,2-linked mannose residue (PIM1). Contrary to PimB, the mannosyltransferase PimA is unable to transfer a mannose residue to the position 6 of the phosphatidyl-myo-inositola of PIM1.<ref>PMID:12068013</ref> <ref>PMID:19638342</ref> | + | [[https://www.uniprot.org/uniprot/PIMA_MYCS2 PIMA_MYCS2]] Catalyzes the addition of a mannose residue from GDP-D-mannose to the position 2 of a phosphatidyl-myo-inositol (PI) to generate a phosphatidyl-myo-inositol bearing an alpha-1,2-linked mannose residue (PIM1). Contrary to PimB, the mannosyltransferase PimA is unable to transfer a mannose residue to the position 6 of the phosphatidyl-myo-inositola of PIM1.<ref>PMID:12068013</ref> <ref>PMID:19638342</ref> |
| | == Evolutionary Conservation == | | == Evolutionary Conservation == |
| | [[Image:Consurf_key_small.gif|200px|right]] | | [[Image:Consurf_key_small.gif|200px|right]] |
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| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| | + | [[Category: Large Structures]] |
| | [[Category: Mycs2]] | | [[Category: Mycs2]] |
| | [[Category: Alzari, P M]] | | [[Category: Alzari, P M]] |
| Structural highlights
Function
[PIMA_MYCS2] Catalyzes the addition of a mannose residue from GDP-D-mannose to the position 2 of a phosphatidyl-myo-inositol (PI) to generate a phosphatidyl-myo-inositol bearing an alpha-1,2-linked mannose residue (PIM1). Contrary to PimB, the mannosyltransferase PimA is unable to transfer a mannose residue to the position 6 of the phosphatidyl-myo-inositola of PIM1.[1] [2]
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
Mycobacterial phosphatidylinositol mannosides (PIMs) and metabolically derived cell wall lipoglycans play important roles in host-pathogen interactions, but their biosynthetic pathways are poorly understood. Here we focus on Mycobacterium smegmatis PimA, an essential enzyme responsible for the initial mannosylation of phosphatidylinositol. The structure of PimA in complex with GDP-mannose shows the two-domain organization and the catalytic machinery typical of GT-B glycosyltransferases. PimA is an amphitrophic enzyme that binds mono-disperse phosphatidylinositol, but its transferase activity is stimulated by high concentrations of non-substrate anionic surfactants, indicating that the early stages of PIM biosynthesis involve lipid-water interfacial catalysis. Based on structural, calorimetric, and mutagenesis studies, we propose a model wherein PimA attaches to the membrane through its N-terminal domain, and this association leads to enzyme activation. Our results reveal a novel mode of phosphatidylinositol recognition and provide a template for the development of potential antimycobacterial compounds.
Molecular recognition and interfacial catalysis by the essential phosphatidylinositol mannosyltransferase PimA from mycobacteria.,Guerin ME, Kordulakova J, Schaeffer F, Svetlikova Z, Buschiazzo A, Giganti D, Gicquel B, Mikusova K, Jackson M, Alzari PM J Biol Chem. 2007 Jul 13;282(28):20705-14. Epub 2007 May 16. PMID:17510062[3]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Kordulakova J, Gilleron M, Mikusova K, Puzo G, Brennan PJ, Gicquel B, Jackson M. Definition of the first mannosylation step in phosphatidylinositol mannoside synthesis. PimA is essential for growth of mycobacteria. J Biol Chem. 2002 Aug 30;277(35):31335-44. Epub 2002 Jun 14. PMID:12068013 doi:10.1074/jbc.M204060200
- ↑ Guerin ME, Kaur D, Somashekar BS, Gibbs S, Gest P, Chatterjee D, Brennan PJ, Jackson M. New insights into the early steps of phosphatidylinositol mannoside biosynthesis in mycobacteria: PimB' is an essential enzyme of Mycobacterium smegmatis. J Biol Chem. 2009 Sep 18;284(38):25687-96. doi: 10.1074/jbc.M109.030593. Epub, 2009 Jul 28. PMID:19638342 doi:http://dx.doi.org/10.1074/jbc.M109.030593
- ↑ Guerin ME, Kordulakova J, Schaeffer F, Svetlikova Z, Buschiazzo A, Giganti D, Gicquel B, Mikusova K, Jackson M, Alzari PM. Molecular recognition and interfacial catalysis by the essential phosphatidylinositol mannosyltransferase PimA from mycobacteria. J Biol Chem. 2007 Jul 13;282(28):20705-14. Epub 2007 May 16. PMID:17510062 doi:10.1074/jbc.M702087200
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