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| | ==Crystal structure of MycP1 with the N-terminal propeptide removed== | | ==Crystal structure of MycP1 with the N-terminal propeptide removed== |
| - | <StructureSection load='4m1z' size='340' side='right' caption='[[4m1z]], [[Resolution|resolution]] 2.25Å' scene=''> | + | <StructureSection load='4m1z' size='340' side='right'caption='[[4m1z]], [[Resolution|resolution]] 2.25Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[4m1z]] is a 4 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=4M1Z OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4M1Z FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[4m1z]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/Mycolicibacterium_smegmatis_MC2_155 Mycolicibacterium smegmatis MC2 155]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4M1Z OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4M1Z FirstGlance]. <br> |
| - | </td></tr><tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">MSMEG_0083, MSMEI_0081 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=246196 MYCS2])</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]] 2.25Å</td></tr> |
| - | <tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Subtilisin Subtilisin], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.4.21.62 3.4.21.62] </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=4m1z FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4m1z OCA], [https://pdbe.org/4m1z PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4m1z RCSB], [https://www.ebi.ac.uk/pdbsum/4m1z PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4m1z 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=4m1z FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4m1z OCA], [http://pdbe.org/4m1z PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4m1z RCSB], [http://www.ebi.ac.uk/pdbsum/4m1z PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4m1z ProSAT]</span></td></tr> | + | |
| | </table> | | </table> |
| | + | == Function == |
| | + | [https://www.uniprot.org/uniprot/MYCP1_MYCS2 MYCP1_MYCS2] May play a dual role in regulation of ESX-1 secretion and virulence. Acts as a protease that cleaves EspB.<ref>PMID:20227664</ref> <ref>PMID:23620593</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: Mycs2]] | + | [[Category: Large Structures]] |
| - | [[Category: Subtilisin]] | + | [[Category: Mycolicibacterium smegmatis MC2 155]] |
| - | [[Category: He, Y]] | + | [[Category: He Y]] |
| - | [[Category: Sun, D M]] | + | [[Category: Sun DM]] |
| - | [[Category: Tian, C L]] | + | [[Category: Tian CL]] |
| - | [[Category: Wang, C L]] | + | [[Category: Wang CL]] |
| - | [[Category: Zang, J Y]] | + | [[Category: Zang JY]] |
| - | [[Category: Esx-1 system]]
| + | |
| - | [[Category: Hydrolase]]
| + | |
| - | [[Category: Membrane-anchored]]
| + | |
| - | [[Category: Propeptide-removed]]
| + | |
| - | [[Category: Serine protease]]
| + | |
| - | [[Category: Subtilisin-like]]
| + | |
| Structural highlights
Function
MYCP1_MYCS2 May play a dual role in regulation of ESX-1 secretion and virulence. Acts as a protease that cleaves EspB.[1] [2]
Publication Abstract from PubMed
Mycosin-1 protease (MycP1) is a serine protease anchored to the inner membrane of Mycobacterium tuberculosis, and is essential in virulence factor secretion through the ESX-1 type VII secretion system (T7SS). Bacterial physiology studies demonstrated that MycP1 plays a dual role in the regulation of ESX-1 secretion and virulence, primarily through cleavage of its secretion substrate EspB. MycP1 contains a putative N-terminal inhibitory propeptide and a catalytic triad of Asp-His-Ser, classic hallmarks of a subtilase family serine protease. The MycP1 propeptide was previously reported to be initially inactive and activated after prolonged incubation. In this study, we have determined crystal structures of MycP1 with (MycP1(2)(4)(-)(4)(2)(2)) and without (MycP1(6)(3)(-)(4)(2)(2)) the propeptide, and conducted EspB cleavage assays using the two proteins. Very high structural similarity was observed in the two crystal structures. Interestingly, protease assays demonstrated positive EspB cleavage for both proteins, indicating that the putative propeptide does not inhibit protease activity. Molecular dynamic simulations showed higher rigidity in regions guarding the entrance to the catalytic site in MycP1(2)(4)(-)(4)(2)(2) than in MycP1(6)(3)(-)(4)(2)(2), suggesting that the putative propeptide might contribute to the conformational stability of the active site cleft and surrounding regions.
The putative propeptide of MycP1 in mycobacterial type VII secretion system does not inhibit protease activity but improves protein stability.,Sun D, Liu Q, He Y, Wang C, Wu F, Tian C, Zang J Protein Cell. 2013 Dec;4(12):921-31. doi: 10.1007/s13238-013-3089-7. Epub 2013, Nov 18. PMID:24248472[3]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Ohol YM, Goetz DH, Chan K, Shiloh MU, Craik CS, Cox JS. Mycobacterium tuberculosis MycP1 protease plays a dual role in regulation of ESX-1 secretion and virulence. Cell Host Microbe. 2010 Mar 18;7(3):210-20. doi: 10.1016/j.chom.2010.02.006. PMID:20227664 doi:http://dx.doi.org/10.1016/j.chom.2010.02.006
- ↑ Solomonson M, Huesgen PF, Wasney GA, Watanabe N, Gruninger RJ, Prehna G, Overall CM, Strynadka NC. Structure of the Mycosin-1 Protease from the Mycobacterial ESX-1 Protein Type VII Secretion System. J Biol Chem. 2013 Jun 14;288(24):17782-90. doi: 10.1074/jbc.M113.462036. Epub, 2013 Apr 25. PMID:23620593 doi:10.1074/jbc.M113.462036
- ↑ Sun D, Liu Q, He Y, Wang C, Wu F, Tian C, Zang J. The putative propeptide of MycP1 in mycobacterial type VII secretion system does not inhibit protease activity but improves protein stability. Protein Cell. 2013 Dec;4(12):921-31. doi: 10.1007/s13238-013-3089-7. Epub 2013, Nov 18. PMID:24248472 doi:http://dx.doi.org/10.1007/s13238-013-3089-7
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