2v2e: Difference between revisions
No edit summary |
No edit summary |
||
| Line 3: | Line 3: | ||
<StructureSection load='2v2e' size='340' side='right'caption='[[2v2e]], [[Resolution|resolution]] 1.68Å' scene=''> | <StructureSection load='2v2e' size='340' side='right'caption='[[2v2e]], [[Resolution|resolution]] 1.68Å' scene=''> | ||
== Structural highlights == | == Structural highlights == | ||
<table><tr><td colspan='2'>[[2v2e]] is a 1 chain structure with sequence from [ | <table><tr><td colspan='2'>[[2v2e]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Saccharomyces_cerevisiae Saccharomyces cerevisiae]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2V2E OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2V2E FirstGlance]. <br> | ||
</td></tr><tr id=' | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.68Å</td></tr> | ||
<tr id=' | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=HEM:PROTOPORPHYRIN+IX+CONTAINING+FE'>HEM</scene>, <scene name='pdbligand=ISZ:4-(DIAZENYLCARBONYL)PYRIDINE'>ISZ</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=2v2e FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2v2e OCA], [https://pdbe.org/2v2e PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2v2e RCSB], [https://www.ebi.ac.uk/pdbsum/2v2e PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2v2e ProSAT]</span></td></tr> | |||
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[ | |||
</table> | </table> | ||
== Function == | |||
[https://www.uniprot.org/uniprot/CCPR_YEAST CCPR_YEAST] Destroys radicals which are normally produced within the cells and which are toxic to biological systems. | |||
== Evolutionary Conservation == | == Evolutionary Conservation == | ||
[[Image:Consurf_key_small.gif|200px|right]] | [[Image:Consurf_key_small.gif|200px|right]] | ||
| Line 35: | Line 36: | ||
__TOC__ | __TOC__ | ||
</StructureSection> | </StructureSection> | ||
[[Category: Large Structures]] | [[Category: Large Structures]] | ||
[[Category: | [[Category: Saccharomyces cerevisiae]] | ||
[[Category: | [[Category: Brown KA]] | ||
[[Category: | [[Category: Macdonald IK]] | ||
[[Category: | [[Category: Metcalfe CL]] | ||
[[Category: | [[Category: Moody PCE]] | ||
[[Category: | [[Category: Raven EL]] | ||
Latest revision as of 18:02, 13 December 2023
Structure of isoniazid (INH) bound to cytochrome c peroxidase mutant N184R Y36AStructure of isoniazid (INH) bound to cytochrome c peroxidase mutant N184R Y36A
Structural highlights
FunctionCCPR_YEAST Destroys radicals which are normally produced within the cells and which are toxic to biological systems. Evolutionary Conservation Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf. Publication Abstract from PubMedIsoniazid (INH, isonicotinic acid hydrazine) is one of only two therapeutic agents effective in treating tuberculosis. This prodrug is activated by the heme enzyme catalase peroxidase (KatG) endogenous to Mycobacterium tuberculosis but the mechanism of activation is poorly understood, in part because the binding interaction has not been properly established. The class I peroxidases ascorbate peroxidase (APX) and cytochrome c peroxidase (CcP) have active site structures very similar to KatG and are also capable of activating isoniazid. We report here the first crystal structures of complexes of isoniazid bound to APX and CcP. These are the first structures of isoniazid bound to any activating enzymes. The structures show that isoniazid binds close to the delta-heme edge in both APX and CcP, although the precise binding orientation varies slightly in the two cases. A second binding site for INH is found in APX at the gamma-heme edge close to the established ascorbate binding site, indicating that the gamma-heme edge can also support the binding of aromatic substrates. We also show that in an active site mutant of soybean APX (W41A) INH can bind directly to the heme iron to become an inhibitor and in a different mode when the distal histidine is replaced by alanine (H42A). These structures provide the first unambiguous evidence for the location of the isoniazid binding site in the class I peroxidases and provide rationalization of isoniazid resistance in naturally occurring KatG mutant strains of M. tuberculosis. The tuberculosis prodrug isoniazid bound to activating peroxidases.,Metcalfe C, Macdonald IK, Murphy EJ, Brown KA, Raven EL, Moody PC J Biol Chem. 2008 Mar 7;283(10):6193-200. Epub 2007 Dec 5. PMID:18056997[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
|
| ||||||||||||||||||