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| | ==RipA Peptidoglycan hydrolase (Rv1477, Mycobacterium tuberculosis) N-terminal domain== | | ==RipA Peptidoglycan hydrolase (Rv1477, Mycobacterium tuberculosis) N-terminal domain== |
| - | <StructureSection load='6ewy' size='340' side='right' caption='[[6ewy]], [[Resolution|resolution]] 2.20Å' scene=''> | + | <StructureSection load='6ewy' size='340' side='right'caption='[[6ewy]], [[Resolution|resolution]] 2.20Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[6ewy]] 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=6EWY OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6EWY FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[6ewy]] 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=6EWY OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6EWY FirstGlance]. <br> |
| - | </td></tr><tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">ripA, Rv1477 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=83332 MYCTU])</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]] 2.2Å</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=6ewy FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6ewy OCA], [http://pdbe.org/6ewy PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6ewy RCSB], [http://www.ebi.ac.uk/pdbsum/6ewy PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6ewy 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=6ewy FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6ewy OCA], [https://pdbe.org/6ewy PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6ewy RCSB], [https://www.ebi.ac.uk/pdbsum/6ewy PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6ewy ProSAT]</span></td></tr> |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/RIPA_MYCTU RIPA_MYCTU]] Peptidoglycan endopeptidase that cleaves the bond between D-glutamate and meso-diaminopimelate. Binds and degrades high-molecular weight peptidoglycan from a number of Actinobacteria; activity is increased in the presence of RpfB and inhibited by PBP1A (ponA1). Required for normal separation of daughter cells after cell division and for cell wall integrity. Required for host cell invasion and intracellular survival in host macrophages.<ref>PMID:16495549</ref> <ref>PMID:17919286</ref> <ref>PMID:18463693</ref> <ref>PMID:20826344</ref> <ref>PMID:21864539</ref> | + | [https://www.uniprot.org/uniprot/RIPA_MYCTU RIPA_MYCTU] Peptidoglycan endopeptidase that cleaves the bond between D-glutamate and meso-diaminopimelate. Binds and degrades high-molecular weight peptidoglycan from a number of Actinobacteria; activity is increased in the presence of RpfB and inhibited by PBP1A (ponA1). Required for normal separation of daughter cells after cell division and for cell wall integrity. Required for host cell invasion and intracellular survival in host macrophages.<ref>PMID:16495549</ref> <ref>PMID:17919286</ref> <ref>PMID:18463693</ref> <ref>PMID:20826344</ref> <ref>PMID:21864539</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: Bourenkov, G]] | + | [[Category: Mycobacterium tuberculosis H37Rv]] |
| - | [[Category: Guy, J]] | + | [[Category: Bourenkov G]] |
| - | [[Category: Schneider, G]] | + | [[Category: Guy J]] |
| - | [[Category: Schnell, R]] | + | [[Category: Schneider G]] |
| - | [[Category: Steiner, E M]] | + | [[Category: Schnell R]] |
| - | [[Category: Periplasmic protein]]
| + | [[Category: Steiner EM]] |
| - | [[Category: Structural protein]]
| + | |
| Structural highlights
Function
RIPA_MYCTU Peptidoglycan endopeptidase that cleaves the bond between D-glutamate and meso-diaminopimelate. Binds and degrades high-molecular weight peptidoglycan from a number of Actinobacteria; activity is increased in the presence of RpfB and inhibited by PBP1A (ponA1). Required for normal separation of daughter cells after cell division and for cell wall integrity. Required for host cell invasion and intracellular survival in host macrophages.[1] [2] [3] [4] [5]
Publication Abstract from PubMed
RipA plays a vital role during cell division of Mycobacterium tuberculosis by degrading the cell wall peptidoglycan at the septum, allowing daughter cell separation. The peptidoglycan degrading activity relies on the NlpC/P60 domain, and as it is potentially harmful when deregulated, spatial and temporal control is necessary in this process. The N-terminal domain of RipA has been proposed to play an inhibitory role blocking the C-terminal NlpC/P60 domain. Accessibility of the active site cysteine residue is however not limited by the presence of the N-terminal domain, but by the lid-module of the inter-domain linker, which is situated in the peptide binding groove of the crystal structures of the catalytic domain. The 2.2 A resolution structure of the N-terminal domain, determined by Se-SAD phasing, reveals an all-alpha-fold with two long alpha-helices, and shows similarity to bacterial periplasmic protein domains with scaffold-building role. Size exclusion chromatography and SAXS experiments are consistent with dimer formation of this domain in solution. The SAXS data from the periplasmic two-domain RipA construct suggest a rigid baton-like structure of the N-terminal module, with the catalytic domain connected by a 24 residue long flexible linker. This flexible linker allows for a catalytic zone, which is part of the spatiotemporal control of peptidoglycan degradation. This article is protected by copyright. All rights reserved.
The Structure of the N-terminal Module of the Cell Wall Hydrolase RipA and its Role in Regulating Catalytic Activity.,Steiner EM, Lyngso J, Guy JE, Bourenkov G, Lindqvist Y, Schneider TR, Pedersen JS, Schneider G, Schnell R Proteins. 2018 May 2. doi: 10.1002/prot.25523. PMID:29722065[6]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Gao LY, Pak M, Kish R, Kajihara K, Brown EJ. A mycobacterial operon essential for virulence in vivo and invasion and intracellular persistence in macrophages. Infect Immun. 2006 Mar;74(3):1757-67. PMID:16495549 doi:10.1128/IAI.74.3.1757-1767.2006
- ↑ Hett EC, Chao MC, Steyn AJ, Fortune SM, Deng LL, Rubin EJ. A partner for the resuscitation-promoting factors of Mycobacterium tuberculosis. Mol Microbiol. 2007 Nov;66(3):658-68. Epub 2007 Oct 4. PMID:17919286 doi:10.1111/j.1365-2958.2007.05945.x
- ↑ Hett EC, Chao MC, Deng LL, Rubin EJ. A mycobacterial enzyme essential for cell division synergizes with resuscitation-promoting factor. PLoS Pathog. 2008 Feb 29;4(2):e1000001. doi: 10.1371/journal.ppat.1000001. PMID:18463693 doi:10.1371/journal.ppat.1000001
- ↑ Ruggiero A, Marasco D, Squeglia F, Soldini S, Pedone E, Pedone C, Berisio R. Structure and functional regulation of RipA, a mycobacterial enzyme essential for daughter cell separation. Structure. 2010 Sep 8;18(9):1184-90. PMID:20826344 doi:10.1016/j.str.2010.06.007
- ↑ Both D, Schneider G, Schnell R. Peptidoglycan Remodeling in Mycobacterium tuberculosis: Comparison of Structures and Catalytic Activities of RipA and RipB. J Mol Biol. 2011 Oct 14;413(1):247-60. Epub 2011 Aug 16. PMID:21864539 doi:10.1016/j.jmb.2011.08.014
- ↑ Steiner EM, Lyngso J, Guy JE, Bourenkov G, Lindqvist Y, Schneider TR, Pedersen JS, Schneider G, Schnell R. The Structure of the N-terminal Module of the Cell Wall Hydrolase RipA and its Role in Regulating Catalytic Activity. Proteins. 2018 May 2. doi: 10.1002/prot.25523. PMID:29722065 doi:http://dx.doi.org/10.1002/prot.25523
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