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2v2e

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Revision as of 16:21, 11 August 2016

STRUCTURE OF ISONIAZID (INH) BOUND TO CYTOCHROME C PEROXIDASE MUTANT N184R Y36A

Structural highlights

2v2e is a 1 chain structure with sequence from Atcc 18824. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Ligands:	,
Related:	1a2f, 1a2g, 1aa4, 1ac4, 1ac8, 1aeb, 1aed, 1aee, 1aef, 1aeg, 1aeh, 1aej, 1aek, 1aem, 1aen, 1aeo, 1aeq, 1aes, 1aet, 1aeu, 1aev, 1bej, 1bek, 1bem, 1bep, 1beq, 1bes, 1bj9, 1bva, 1cca, 1ccb, 1ccc, 1cce, 1ccg, 1cci, 1ccj, 1cck, 1ccl, 1ccp, 1cmp, 1cmq, 1cmt, 1cmu, 1cpd, 1cpe, 1cpf, 1cpg, 1cyf, 1dcc, 1dj1, 1dj5, 1ds4, 1dse, 1dsg, 1dso, 1dsp, 1ebe, 1jci, 1jdr, 1kok, 1krj, 1kxm, 1kxn, 1mk8, 1mkq, 1mkr, 1ml2, 1ryc, 1s6v, 1sdq, 1sog, 1stq, 1u74, 1u75, 1z53, 1zby, 1zbz, 2b0z, 2b10, 2b11, 2b12, 2bcn, 2ccp, 2cep, 2cyp, 2gb8, 2pcb, 2pcc, 2v23, 3ccp, 3ccx, 4ccp, 4ccx, 5ccp, 6ccp, 7ccp
Activity:	Cytochrome-c peroxidase, with EC number 1.11.1.5
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

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 PubMed

Isoniazid (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.

References

↑ Metcalfe C, Macdonald IK, Murphy EJ, Brown KA, Raven EL, Moody PC. The tuberculosis prodrug isoniazid bound to activating peroxidases. J Biol Chem. 2008 Mar 7;283(10):6193-200. Epub 2007 Dec 5. PMID:18056997 doi:10.1074/jbc.M707412200

1 Structural highlights
2 Evolutionary Conservation
3 Publication Abstract from PubMed
4 See Also
5 References

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/2v2e"

@@ Line 1: / Line 1: @@
 ==STRUCTURE OF ISONIAZID (INH) BOUND TO CYTOCHROME C PEROXIDASE MUTANT N184R Y36A==
 <StructureSection load='2v2e' size='340' side='right' caption='[[2v2e]], [[Resolution|resolution]] 1.68&Aring;' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[2v2e]] is a 1 chain structure with sequence from [http://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 [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2V2E FirstGlance]. <br>
+<table><tr><td colspan='2'>[[2v2e]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Atcc_18824 Atcc 18824]. 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 [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2V2E FirstGlance]. <br>
 </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=HEM:PROTOPORPHYRIN+IX+CONTAINING+FE'>HEM</scene>, <scene name='pdbligand=ISZ:4-(DIAZENYLCARBONYL)PYRIDINE'>ISZ</scene></td></tr>
 <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[1a2f|1a2f]], [[1a2g|1a2g]], [[1aa4|1aa4]], [[1ac4|1ac4]], [[1ac8|1ac8]], [[1aeb|1aeb]], [[1aed|1aed]], [[1aee|1aee]], [[1aef|1aef]], [[1aeg|1aeg]], [[1aeh|1aeh]], [[1aej|1aej]], [[1aek|1aek]], [[1aem|1aem]], [[1aen|1aen]], [[1aeo|1aeo]], [[1aeq|1aeq]], [[1aes|1aes]], [[1aet|1aet]], [[1aeu|1aeu]], [[1aev|1aev]], [[1bej|1bej]], [[1bek|1bek]], [[1bem|1bem]], [[1bep|1bep]], [[1beq|1beq]], [[1bes|1bes]], [[1bj9|1bj9]], [[1bva|1bva]], [[1cca|1cca]], [[1ccb|1ccb]], [[1ccc|1ccc]], [[1cce|1cce]], [[1ccg|1ccg]], [[1cci|1cci]], [[1ccj|1ccj]], [[1cck|1cck]], [[1ccl|1ccl]], [[1ccp|1ccp]], [[1cmp|1cmp]], [[1cmq|1cmq]], [[1cmt|1cmt]], [[1cmu|1cmu]], [[1cpd|1cpd]], [[1cpe|1cpe]], [[1cpf|1cpf]], [[1cpg|1cpg]], [[1cyf|1cyf]], [[1dcc|1dcc]], [[1dj1|1dj1]], [[1dj5|1dj5]], [[1ds4|1ds4]], [[1dse|1dse]], [[1dsg|1dsg]], [[1dso|1dso]], [[1dsp|1dsp]], [[1ebe|1ebe]], [[1jci|1jci]], [[1jdr|1jdr]], [[1kok|1kok]], [[1krj|1krj]], [[1kxm|1kxm]], [[1kxn|1kxn]], [[1mk8|1mk8]], [[1mkq|1mkq]], [[1mkr|1mkr]], [[1ml2|1ml2]], [[1ryc|1ryc]], [[1s6v|1s6v]], [[1sdq|1sdq]], [[1sog|1sog]], [[1stq|1stq]], [[1u74|1u74]], [[1u75|1u75]], [[1z53|1z53]], [[1zby|1zby]], [[1zbz|1zbz]], [[2b0z|2b0z]], [[2b10|2b10]], [[2b11|2b11]], [[2b12|2b12]], [[2bcn|2bcn]], [[2ccp|2ccp]], [[2cep|2cep]], [[2cyp|2cyp]], [[2gb8|2gb8]], [[2pcb|2pcb]], [[2pcc|2pcc]], [[2v23|2v23]], [[3ccp|3ccp]], [[3ccx|3ccx]], [[4ccp|4ccp]], [[4ccx|4ccx]], [[5ccp|5ccp]], [[6ccp|6ccp]], [[7ccp|7ccp]]</td></tr>
 <tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Cytochrome-c_peroxidase Cytochrome-c peroxidase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=1.11.1.5 1.11.1.5] </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=2v2e FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2v2e OCA], [http://www.rcsb.org/pdb/explore.do?structureId=2v2e RCSB], [http://www.ebi.ac.uk/pdbsum/2v2e 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=2v2e FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2v2e OCA], [http://pdbe.org/2v2e PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=2v2e RCSB], [http://www.ebi.ac.uk/pdbsum/2v2e PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=2v2e ProSAT]</span></td></tr>
 </table>
 == Evolutionary Conservation ==
@@ Line 16: / Line 17: @@
     <text>to colour the structure by Evolutionary Conservation</text>
   </jmolCheckbox>
-</jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/chain_selection.php?pdb_ID=2ata ConSurf].
+</jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/main_output.php?pdb_ID=2v2e ConSurf].
 <div style="clear:both"></div>
 <div style="background-color:#fffaf0;">
@@ Line 26: / Line 27: @@
 From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
 </div>
+<div class="pdbe-citations 2v2e" style="background-color:#fffaf0;"></div>
 ==See Also==
@@ Line 33: / Line 35: @@
 __TOC__
 </StructureSection>
+[[Category: Atcc 18824]]
 [[Category: Cytochrome-c peroxidase]]
-[[Category: Saccharomyces cerevisiae]]
 [[Category: Brown, K A]]
 [[Category: Macdonald, I K]]

2v2e

From Proteopedia

Revision as of 16:21, 11 August 2016

STRUCTURE OF ISONIAZID (INH) BOUND TO CYTOCHROME C PEROXIDASE MUTANT N184R Y36A

Structural highlights

Evolutionary Conservation

Publication Abstract from PubMed

See Also

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

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