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| | ==High resolution structure of MeT1 from Mycobacterium hassiacum in complex with 3-methoxy-1,2-propanediol.== | | ==High resolution structure of MeT1 from Mycobacterium hassiacum in complex with 3-methoxy-1,2-propanediol.== |
| - | <StructureSection load='6h40' size='340' side='right' caption='[[6h40]], [[Resolution|resolution]] 1.05Å' scene=''> | + | <StructureSection load='6h40' size='340' side='right'caption='[[6h40]], [[Resolution|resolution]] 1.05Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[6h40]] is a 1 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6H40 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6H40 FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[6h40]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Mycolicibacterium_hassiacum_DSM_44199 Mycolicibacterium hassiacum DSM 44199]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6H40 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6H40 FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=FW5:(2~{S})-3-methoxypropane-1,2-diol'>FW5</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene>, <scene name='pdbligand=SAH:S-ADENOSYL-L-HOMOCYSTEINE'>SAH</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]] 1.053Å</td></tr> |
| - | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[6g7d|6g7d]], [[6g80|6g80]]</td></tr>
| + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=FW5:(2~{S})-3-methoxypropane-1,2-diol'>FW5</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene>, <scene name='pdbligand=SAH:S-ADENOSYL-L-HOMOCYSTEINE'>SAH</scene></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=6h40 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6h40 OCA], [http://pdbe.org/6h40 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6h40 RCSB], [http://www.ebi.ac.uk/pdbsum/6h40 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6h40 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=6h40 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6h40 OCA], [https://pdbe.org/6h40 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6h40 RCSB], [https://www.ebi.ac.uk/pdbsum/6h40 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6h40 ProSAT]</span></td></tr> |
| | </table> | | </table> |
| | + | == Function == |
| | + | [https://www.uniprot.org/uniprot/MET1_MYCHD MET1_MYCHD] Involved in the biosynthesis of 3-O-methylmannose polysaccharides (MMP), which are intracellular polymethylated polysaccharides implicated in the modulation of fatty acid metabolism in non-tuberculous mycobacteria (PubMed:30606802). Specifically methylates the 1-OH position of 3,3'-di-O-methyl-4alpha-mannobiose, a probable early precursor of MMP, yielding the reducing end dimannoside of MMP (PubMed:30606802).<ref>PMID:30606802</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: Pereira, P J.B]] | + | [[Category: Large Structures]] |
| - | [[Category: Ripoll-Rozada, J]] | + | [[Category: Mycolicibacterium hassiacum DSM 44199]] |
| - | [[Category: 3-o-methyltransferase]] | + | [[Category: Pereira PJB]] |
| - | [[Category: Transferase]] | + | [[Category: Ripoll-Rozada J]] |
| Structural highlights
6h40 is a 1 chain structure with sequence from Mycolicibacterium hassiacum DSM 44199. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
| | Method: | X-ray diffraction, Resolution 1.053Å |
| Ligands: | , , , , |
| Resources: | FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT |
Function
MET1_MYCHD Involved in the biosynthesis of 3-O-methylmannose polysaccharides (MMP), which are intracellular polymethylated polysaccharides implicated in the modulation of fatty acid metabolism in non-tuberculous mycobacteria (PubMed:30606802). Specifically methylates the 1-OH position of 3,3'-di-O-methyl-4alpha-mannobiose, a probable early precursor of MMP, yielding the reducing end dimannoside of MMP (PubMed:30606802).[1]
Publication Abstract from PubMed
Mycobacteria are a wide group of organisms that includes strict pathogens, such as Mycobacterium tuberculosis, as well as environmental species known as nontuberculous mycobacteria (NTM), some of which-namely Mycobacterium avium-are important opportunistic pathogens. In addition to a distinctive cell envelope mediating critical interactions with the host immune system and largely responsible for their formidable resistance to antimicrobials, mycobacteria synthesize rare intracellular polymethylated polysaccharides implicated in the modulation of fatty acid metabolism, thus critical players in cell envelope assembly. These are the 6-O-methylglucose lipopolysaccharides (MGLP) ubiquitously detected across the Mycobacterium genus, and the 3-O-methylmannose polysaccharides (MMP) identified only in NTM. The polymethylated nature of these polysaccharides renders the intervening methyltransferases essential for their optimal function. Although the knowledge of MGLP biogenesis is greater than that of MMP biosynthesis, the methyltransferases of both pathways remain uncharacterized. Here, we report the identification and characterization of a unique S-adenosyl-l-methionine-dependent sugar 1-O-methyltransferase (MeT1) from Mycobacterium hassiacum that specifically blocks the 1-OH position of 3,3'-di-O-methyl-4alpha-mannobiose, a probable early precursor of MMP, which we chemically synthesized. The high-resolution 3D structure of MeT1 in complex with its exhausted cofactor, S-adenosyl-l-homocysteine, together with mutagenesis studies and molecular docking simulations, unveiled the enzyme's reaction mechanism. The functional and structural properties of this unique sugar methyltransferase further our knowledge of MMP biosynthesis and provide important tools to dissect the role of MMP in NTM physiology and resilience.
Biosynthesis of mycobacterial methylmannose polysaccharides requires a unique 1-O-methyltransferase specific for 3-O-methylated mannosides.,Ripoll-Rozada J, Costa M, Manso JA, Maranha A, Miranda V, Sequeira A, Ventura MR, Macedo-Ribeiro S, Pereira PJB, Empadinhas N Proc Natl Acad Sci U S A. 2019 Jan 15;116(3):835-844. doi:, 10.1073/pnas.1813450116. Epub 2019 Jan 3. PMID:30606802[2]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Ripoll-Rozada J, Costa M, Manso JA, Maranha A, Miranda V, Sequeira A, Ventura MR, Macedo-Ribeiro S, Pereira PJB, Empadinhas N. Biosynthesis of mycobacterial methylmannose polysaccharides requires a unique 1-O-methyltransferase specific for 3-O-methylated mannosides. Proc Natl Acad Sci U S A. 2019 Jan 15;116(3):835-844. doi:, 10.1073/pnas.1813450116. Epub 2019 Jan 3. PMID:30606802 doi:http://dx.doi.org/10.1073/pnas.1813450116
- ↑ Ripoll-Rozada J, Costa M, Manso JA, Maranha A, Miranda V, Sequeira A, Ventura MR, Macedo-Ribeiro S, Pereira PJB, Empadinhas N. Biosynthesis of mycobacterial methylmannose polysaccharides requires a unique 1-O-methyltransferase specific for 3-O-methylated mannosides. Proc Natl Acad Sci U S A. 2019 Jan 15;116(3):835-844. doi:, 10.1073/pnas.1813450116. Epub 2019 Jan 3. PMID:30606802 doi:http://dx.doi.org/10.1073/pnas.1813450116
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