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| - | | + | #REDIRECT [[5syj]] This PDB entry is obsolete and replaced by 5syj |
| - | ==Crystal Structure of BpKatG (D141A) in complex with Isoniazid==
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| - | <StructureSection load='4kwq' size='340' side='right' caption='[[4kwq]], [[Resolution|resolution]] 1.88Å' scene=''>
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| - | == Structural highlights ==
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| - | <table><tr><td colspan='2'>[[4kwq]] is a 2 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4KWQ OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4KWQ FirstGlance]. <br>
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| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=HEM:PROTOPORPHYRIN+IX+CONTAINING+FE'>HEM</scene>, <scene name='pdbligand=MPD:(4S)-2-METHYL-2,4-PENTANEDIOL'>MPD</scene>, <scene name='pdbligand=NA:SODIUM+ION'>NA</scene>, <scene name='pdbligand=NIZ:PYRIDINE-4-CARBOHYDRAZIDE'>NIZ</scene></td></tr>
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| - | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[4ka5|4ka5]], [[4ka6|4ka6]]</td></tr>
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| - | <tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Catalase_peroxidase Catalase peroxidase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=1.11.1.21 1.11.1.21] </span></td></tr>
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| - | <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=4kwq FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4kwq OCA], [http://pdbe.org/4kwq PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4kwq RCSB], [http://www.ebi.ac.uk/pdbsum/4kwq PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4kwq ProSAT]</span></td></tr>
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| - | </table>
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| - | == Function ==
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| - | [[http://www.uniprot.org/uniprot/B7CLB5_BURPE B7CLB5_BURPE]] Bifunctional enzyme with both catalase and broad-spectrum peroxidase activity (By similarity).[HAMAP-Rule:MF_01961]
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| - | <div style="background-color:#fffaf0;">
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| - | == Publication Abstract from PubMed ==
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| - | Isonicotinic acid hydrazide (isoniazid or INH) is a front line antitubercular pro-drug that is converted to its active form, isonicotinyl-NAD, by the bacterial catalase-peroxidase KatG. Understanding the role of KatG in the INH activation process has been hampered by a lack of knowledge of the actual drug binding site. In this work, we have investigated the binding of INH in the main access channel of KatG with a combination of molecular dynamics, using an enhanced-sampling technique (metadynamics), X-ray crystallography, and site-directed mutagenesis. The metadynamics simulations show that there are several weak drug binding sites along the access channel. Moreover, the simulations evidence that complete entrance to the heme active site is impeded by an aspartate residue (D141) located above the heme. This has been confirmed by structural and functional analysis of the D141A mutant, leading to the first X-ray crystallography evidence of INH at the heme access channel.
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| - | Binding of the Antitubercular Pro-Drug Isoniazid in the Heme Access Channel of Catalase-Peroxidase (KatG). A Combined Structural and Metadynamics Investigation.,Vidossich P, Loewen PC, Carpena X, Fiorin G, Fita I, Rovira C J Phys Chem B. 2014 Mar 20;118(11):2924-31. doi: 10.1021/jp4123425. Epub 2014 Mar, 7. PMID:24568093<ref>PMID:24568093</ref>
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| - | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
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| - | </div>
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| - | <div class="pdbe-citations 4kwq" style="background-color:#fffaf0;"></div>
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| - | == References ==
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| - | <references/>
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| - | __TOC__
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| - | </StructureSection>
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| - | [[Category: Catalase peroxidase]]
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| - | [[Category: Carpena, X]]
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| - | [[Category: Fita, I]]
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| - | [[Category: Loewen, P C]]
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| - | [[Category: Alpha protein]]
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| - | [[Category: Catalase-peroxidase oxidoreductase]]
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| - | [[Category: Isoniazid binding]]
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| - | [[Category: Katg]]
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| - | [[Category: Oxidoreductase]]
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| - | [[Category: Triple aminoacid adduct]]
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