4q4t

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(Difference between revisions)

Revision as of 20:01, 4 August 2016

Structure of the Resuscitation Promoting Factor Interacting protein RipA mutated at E444

Structural highlights

4q4t is a 1 chain structure. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Ligands:	,
Related:	4q4n, 4q4g
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

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 is a key cysteine protease of Mycobacterium tuberculosis as it is responsible for bacterial daughter-cell separation. Although it is an important target for antimicrobial development, its mechanism of action and its interaction pattern with its substrate are hitherto unknown. By combining crystallographic and mutational studies with functional assays and molecular modelling, it is shown that the catalytic activity of the enzyme relies on a Cys-His-Glu triad and the impact of the mutation of each residue of the triad on the structure and function of RipA is analysed. Unexpectedly, the crystallographic analyses reveal that mutation of the glutamic acid to alanine results in inversion of the configuration of the catalytic cysteine. The consequent burial of the catalytic cysteine side chain explains the enzyme inactivation upon mutation. These data point to a novel role of the acidic residue often present in the triad of cysteine proteases as a supervisor of cysteine configuration through preservation of the local structural integrity.

Mutational and structural study of RipA, a key enzyme in Mycobacterium tuberculosis cell division: evidence for the L-to-D inversion of configuration of the catalytic cysteine.,Squeglia F, Ruggiero A, Romano M, Vitagliano L, Berisio R Acta Crystallogr D Biol Crystallogr. 2014 Sep 1;70(Pt 9):2295-300. doi:, 10.1107/S1399004714013674. Epub 2014 Aug 29. PMID:25195744^[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
↑ Squeglia F, Ruggiero A, Romano M, Vitagliano L, Berisio R. Mutational and structural study of RipA, a key enzyme in Mycobacterium tuberculosis cell division: evidence for the L-to-D inversion of configuration of the catalytic cysteine. Acta Crystallogr D Biol Crystallogr. 2014 Sep 1;70(Pt 9):2295-300. doi:, 10.1107/S1399004714013674. Epub 2014 Aug 29. PMID:25195744 doi:http://dx.doi.org/10.1107/S1399004714013674

1 Structural highlights
2 Function
3 Publication Abstract from PubMed
4 References

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/4q4t"

@@ Line 1: / Line 1: @@
 ==Structure of the Resuscitation Promoting Factor Interacting protein RipA mutated at E444==
 <StructureSection load='4q4t' size='340' side='right' caption='[[4q4t]], [[Resolution|resolution]] 1.63&Aring;' scene=''>
@@ Line 5: / Line 6: @@
 </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=FMT:FORMIC+ACID'>FMT</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene></td></tr>
 <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[4q4n|4q4n]], [[4q4g|4q4g]]</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=4q4t FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4q4t OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4q4t RCSB], [http://www.ebi.ac.uk/pdbsum/4q4t PDBsum]</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=4q4t FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4q4t OCA], [http://pdbe.org/4q4t PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4q4t RCSB], [http://www.ebi.ac.uk/pdbsum/4q4t PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4q4t ProSAT]</span></td></tr>
 </table>
 == Function ==
@@ Line 17: / Line 18: @@
 From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
 </div>
+<div class="pdbe-citations 4q4t" style="background-color:#fffaf0;"></div>
 == References ==
 <references/>

4q4t

From Proteopedia

Revision as of 20:01, 4 August 2016

Structure of the Resuscitation Promoting Factor Interacting protein RipA mutated at E444

Structural highlights

Function

Publication Abstract from PubMed

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

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