4yf6: Difference between revisions
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==Crystal structure of oxidised Rv1284== | |||
<StructureSection load='4yf6' size='340' side='right'caption='[[4yf6]], [[Resolution|resolution]] 3.00Å' scene=''> | |||
== Structural highlights == | |||
<table><tr><td colspan='2'>[[4yf6]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/Mycobacterium_tuberculosis_CDC1551 Mycobacterium tuberculosis CDC1551]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4YF6 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4YF6 FirstGlance]. <br> | |||
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 3.002Å</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=MG:MAGNESIUM+ION'>MG</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</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=4yf6 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4yf6 OCA], [https://pdbe.org/4yf6 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4yf6 RCSB], [https://www.ebi.ac.uk/pdbsum/4yf6 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4yf6 ProSAT]</span></td></tr> | |||
</table> | |||
== Function == | |||
[https://www.uniprot.org/uniprot/MTCA1_MYCTO MTCA1_MYCTO] Catalyzes the reversible hydration of carbon dioxide to form bicarbonate. | |||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
The mycobacterial enzyme Rv1284 is a member of the beta-carbonic anhydrase family that has been deemed essential for survival of the pathogen. The active site cavity of this dimeric protein is characterised by an exceptionally small volume and harbours a catalytic zinc ion coordinated by two cysteine and one histidine residue side chains. Using the natural products polycarpine and emodin as chemical probes in crystallographic experiments and stopped-flow enzyme assays, we describe here that the catalytic activity can be reversibly inhibited by oxidation. Oxidative conditions lead to removal of one of the active site cysteine residues from the coordination sphere of the catalytic metal ion by engagement in a disulphide bond with another cysteine residue close by. The subsequent loss of the metal ion, which is supported by crystallographic analysis, may thus render the protein catalytically inactive. The oxidative inhibition of Rv1284 can be reversed by exposing the protein to reducing conditions. Since the physical size of the chemical probes used in this study substantially exceeds the active site volume, we hypothesised that these compounds exert their effects from a surface-bound location and identified tyrosine 120 as a critical residue for oxidative inactivation. These findings link conditions of oxidative stress to pH homeostasis of the pathogen. Since oxidative stress and acidification are defence mechanisms employed by the innate immune system of the host, we suggest that Rv1284 may be a component of the mycobacterial survival strategy. This article is protected by copyright. All rights reserved. | |||
Chemical probing suggests Redox-regulation of the carbonic anhydrase activity of mycobacterial Rv1284.,Nienaber L, Cave-Freeman E, Cross M, Mason L, Bailey UM, Amani P, Davis R, Taylor P, Hofmann A FEBS J. 2015 Apr 30. doi: 10.1111/febs.13313. PMID:25929542<ref>PMID:25929542</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
[[Category: | </div> | ||
[[Category: Hofmann | <div class="pdbe-citations 4yf6" style="background-color:#fffaf0;"></div> | ||
==See Also== | |||
*[[Carbonic anhydrase 3D structures|Carbonic anhydrase 3D structures]] | |||
== References == | |||
<references/> | |||
__TOC__ | |||
</StructureSection> | |||
[[Category: Large Structures]] | |||
[[Category: Mycobacterium tuberculosis CDC1551]] | |||
[[Category: Hofmann A]] | |||
Latest revision as of 10:58, 27 September 2023
Crystal structure of oxidised Rv1284Crystal structure of oxidised Rv1284
Structural highlights
FunctionMTCA1_MYCTO Catalyzes the reversible hydration of carbon dioxide to form bicarbonate. Publication Abstract from PubMedThe mycobacterial enzyme Rv1284 is a member of the beta-carbonic anhydrase family that has been deemed essential for survival of the pathogen. The active site cavity of this dimeric protein is characterised by an exceptionally small volume and harbours a catalytic zinc ion coordinated by two cysteine and one histidine residue side chains. Using the natural products polycarpine and emodin as chemical probes in crystallographic experiments and stopped-flow enzyme assays, we describe here that the catalytic activity can be reversibly inhibited by oxidation. Oxidative conditions lead to removal of one of the active site cysteine residues from the coordination sphere of the catalytic metal ion by engagement in a disulphide bond with another cysteine residue close by. The subsequent loss of the metal ion, which is supported by crystallographic analysis, may thus render the protein catalytically inactive. The oxidative inhibition of Rv1284 can be reversed by exposing the protein to reducing conditions. Since the physical size of the chemical probes used in this study substantially exceeds the active site volume, we hypothesised that these compounds exert their effects from a surface-bound location and identified tyrosine 120 as a critical residue for oxidative inactivation. These findings link conditions of oxidative stress to pH homeostasis of the pathogen. Since oxidative stress and acidification are defence mechanisms employed by the innate immune system of the host, we suggest that Rv1284 may be a component of the mycobacterial survival strategy. This article is protected by copyright. All rights reserved. Chemical probing suggests Redox-regulation of the carbonic anhydrase activity of mycobacterial Rv1284.,Nienaber L, Cave-Freeman E, Cross M, Mason L, Bailey UM, Amani P, Davis R, Taylor P, Hofmann A FEBS J. 2015 Apr 30. doi: 10.1111/febs.13313. PMID:25929542[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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