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| | ==Mycobacterial membrane protein MmpL11D2== | | ==Mycobacterial membrane protein MmpL11D2== |
| - | <StructureSection load='4y0l' size='340' side='right' caption='[[4y0l]], [[Resolution|resolution]] 2.40Å' scene=''> | + | <StructureSection load='4y0l' size='340' side='right'caption='[[4y0l]], [[Resolution|resolution]] 2.40Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[4y0l]] is a 1 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4Y0L OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4Y0L FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[4y0l]] 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=4Y0L OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4Y0L FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=IOD:IODIDE+ION'>IOD</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</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]] 2.4Å</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=4y0l FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4y0l OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4y0l RCSB], [http://www.ebi.ac.uk/pdbsum/4y0l PDBsum]</span></td></tr> | + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=IOD:IODIDE+ION'>IOD</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene></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=4y0l FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4y0l OCA], [https://pdbe.org/4y0l PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4y0l RCSB], [https://www.ebi.ac.uk/pdbsum/4y0l PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4y0l ProSAT]</span></td></tr> |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/MMPLB_MYCTU MMPLB_MYCTU]] Part of a heme-iron acquisition system. Receives heme from the heme-binding protein Rv0203 and transports it into the mycobacterial cell. Contributes to virulence.<ref>PMID:15908378</ref> <ref>PMID:21383189</ref> <ref>PMID:23760277</ref> Could also transport the mycolic acid-containing lipids monomeromycolyl diacylglycerol (MMDAG) and mycolate ester wax (WE) to the bacterial surface.<ref>PMID:23836904</ref> | + | [https://www.uniprot.org/uniprot/MMPLB_MYCTU MMPLB_MYCTU] Part of a heme-iron acquisition system. Receives heme from the heme-binding protein Rv0203 and transports it into the mycobacterial cell. Contributes to virulence.<ref>PMID:15908378</ref> <ref>PMID:21383189</ref> <ref>PMID:23760277</ref> Could also transport the mycolic acid-containing lipids monomeromycolyl diacylglycerol (MMDAG) and mycolate ester wax (WE) to the bacterial surface.<ref>PMID:23836904</ref> |
| - | <div style="background-color:#fffaf0;">
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| - | == Publication Abstract from PubMed ==
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| - | Mycobacterium tuberculosis mycobacterial membrane protein large (MmpL) proteins are important in substrate transport across the inner membrane. Here, we show that MmpL proteins are classified into two phylogenetic clusters, where MmpL cluster II contains three soluble domains (D1, D2, and D3) and has two full-length members, MmpL3 and MmpL11. Significantly, MmpL3 is currently the most druggable M. tuberculosis target. We have solved the 2.4-A MmpL11-D2 crystal structure, revealing structural homology to periplasmic porter subdomains of RND (multidrug) transporters. The resulting predicted cluster II MmpL membrane topology has D1 and D2 residing, and possibly interacting, within the periplasm. Crosslinking and biolayer interferometry experiments confirm that cluster II D1 and D2 bind with weak affinities, and guided D1-D2 heterodimeric model assemblies. The predicted full-length MmpL3 and MmpL11 structural models reveal key substrate binding and transport residues, and may serve as templates to set the stage for in silico anti-tuberculosis drug development.
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| - | The Structure and Interactions of Periplasmic Domains of Crucial MmpL Membrane Proteins from Mycobacterium tuberculosis.,Chim N, Torres R, Liu Y, Capri J, Batot G, Whitelegge JP, Goulding CW Chem Biol. 2015 Aug 20;22(8):1098-107. doi: 10.1016/j.chembiol.2015.07.013. Epub , 2015 Aug 13. PMID:26278184<ref>PMID:26278184</ref>
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| - | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
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| - | </div>
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| | == References == | | == References == |
| | <references/> | | <references/> |
| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Chim, N]] | + | [[Category: Large Structures]] |
| - | [[Category: Goulding, C W]] | + | [[Category: Mycobacterium tuberculosis H37Rv]] |
| - | [[Category: Torres, R]] | + | [[Category: Chim N]] |
| - | [[Category: Membrane protein]] | + | [[Category: Goulding CW]] |
| - | [[Category: Rnd family]] | + | [[Category: Torres R]] |
| Structural highlights
Function
MMPLB_MYCTU Part of a heme-iron acquisition system. Receives heme from the heme-binding protein Rv0203 and transports it into the mycobacterial cell. Contributes to virulence.[1] [2] [3] Could also transport the mycolic acid-containing lipids monomeromycolyl diacylglycerol (MMDAG) and mycolate ester wax (WE) to the bacterial surface.[4]
References
- ↑ Domenech P, Reed MB, Barry CE 3rd. Contribution of the Mycobacterium tuberculosis MmpL protein family to virulence and drug resistance. Infect Immun. 2005 Jun;73(6):3492-501. PMID:15908378 doi:http://dx.doi.org/10.1128/IAI.73.6.3492-3501.2005
- ↑ Tullius MV, Harmston CA, Owens CP, Chim N, Morse RP, McMath LM, Iniguez A, Kimmey JM, Sawaya MR, Whitelegge JP, Horwitz MA, Goulding CW. Discovery and characterization of a unique mycobacterial heme acquisition system. Proc Natl Acad Sci U S A. 2011 Mar 7. PMID:21383189 doi:10.1073/pnas.1009516108
- ↑ Owens CP, Chim N, Graves AB, Harmston CA, Iniguez A, Contreras H, Liptak MD, Goulding CW. The Mycobacterium tuberculosis secreted protein Rv0203 transfers heme to membrane proteins MmpL3 and MmpL11. J Biol Chem. 2013 Jul 26;288(30):21714-28. doi: 10.1074/jbc.M113.453076. Epub, 2013 Jun 11. PMID:23760277 doi:http://dx.doi.org/10.1074/jbc.M113.453076
- ↑ Pacheco SA, Hsu FF, Powers KM, Purdy GE. MmpL11 protein transports mycolic acid-containing lipids to the mycobacterial cell wall and contributes to biofilm formation in Mycobacterium smegmatis. J Biol Chem. 2013 Aug 16;288(33):24213-22. doi: 10.1074/jbc.M113.473371. Epub, 2013 Jul 8. PMID:23836904 doi:http://dx.doi.org/10.1074/jbc.M113.473371
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