5syj: Difference between revisions

Revision as of 12:51, 4 October 2023

Crystal structure of the D141A variant of B. pseudomallei KatGin complex with isoniazid

Structural highlights

5syj is a 2 chain structure with sequence from Burkholderia pseudomallei 1710b. This structure supersedes the now removed PDB entry 4kwq. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:	X-ray diffraction, Resolution 1.88Å
Ligands:	CL, HEM, MPD, NA, NIZ, PO4
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

KATG_BURP1 Bifunctional enzyme with both catalase and broad-spectrum peroxidase activity.

Publication Abstract from PubMed

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.

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^[1]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

References

↑ Vidossich P, Loewen PC, Carpena X, Fiorin G, Fita I, Rovira C. Binding of the Antitubercular Pro-Drug Isoniazid in the Heme Access Channel of Catalase-Peroxidase (KatG). A Combined Structural and Metadynamics Investigation. J Phys Chem B. 2014 Mar 20;118(11):2924-31. doi: 10.1021/jp4123425. Epub 2014 Mar, 7. PMID:24568093 doi:https://dx.doi.org/10.1021/jp4123425

Proteopedia Page Contributors and Editors (what is this?)

OCA

[1] Vidossich P, Loewen PC, Carpena X, Fiorin G, Fita I, Rovira C. Binding of the Antitubercular Pro-Drug Isoniazid in the Heme Access Channel of Catalase-Peroxidase (KatG). A Combined Structural and Metadynamics Investigation. J Phys Chem B. 2014 Mar 20;118(11):2924-31. doi: 10.1021/jp4123425. Epub 2014 Mar, 7. PMID:24568093 doi:https://dx.doi.org/10.1021/jp4123425

[1]

@@ Line 3: / Line 3: @@
 <StructureSection load='5syj' size='340' side='right'caption='[[5syj]], [[Resolution|resolution]] 1.88&Aring;' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[5syj]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Burp1 Burp1]. This structure supersedes the now removed PDB entry [http://oca.weizmann.ac.il/oca-bin/send-pdb?obs=1&id=4kwq 4kwq]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5SYJ OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5SYJ FirstGlance]. <br>
+<table><tr><td colspan='2'>[[5syj]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Burkholderia_pseudomallei_1710b Burkholderia pseudomallei 1710b]. This structure supersedes the now removed PDB entry [http://oca.weizmann.ac.il/oca-bin/send-pdb?obs=1&id=4kwq 4kwq]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5SYJ OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5SYJ FirstGlance]. <br>
-</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>, <scene name='pdbligand=PO4:PHOSPHATE+ION'>PO4</scene></td></tr>
+</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.88&#8491;</td></tr>
-<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">katG, BURPS1710b_3366 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=320372 BURP1])</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=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>, <scene name='pdbligand=PO4:PHOSPHATE+ION'>PO4</scene></td></tr>
-<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>
+<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=5syj FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5syj OCA], [https://pdbe.org/5syj PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5syj RCSB], [https://www.ebi.ac.uk/pdbsum/5syj PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5syj ProSAT]</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=5syj FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5syj OCA], [http://pdbe.org/5syj PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5syj RCSB], [http://www.ebi.ac.uk/pdbsum/5syj PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5syj ProSAT]</span></td></tr>
 </table>
 == Function ==
-[[http://www.uniprot.org/uniprot/KATG_BURP1 KATG_BURP1]] Bifunctional enzyme with both catalase and broad-spectrum peroxidase activity.
+[https://www.uniprot.org/uniprot/KATG_BURP1 KATG_BURP1] Bifunctional enzyme with both catalase and broad-spectrum peroxidase activity.
 <div style="background-color:#fffaf0;">
 == Publication Abstract from PubMed ==
@@ Line 27: / Line 26: @@
 __TOC__
 </StructureSection>
-[[Category: Burp1]]
+[[Category: Burkholderia pseudomallei 1710b]]
-[[Category: Catalase peroxidase]]
 [[Category: Large Structures]]
-[[Category: Loewen, P C]]
+[[Category: Loewen PC]]
-[[Category: Catalase-peroxidase]]
-[[Category: Isoniazid]]
-[[Category: Katg]]
-[[Category: Oxidoreductase]]

5syj: Difference between revisions

Revision as of 12:51, 4 October 2023

Crystal structure of the D141A variant of B. pseudomallei KatGin complex with isoniazid

Structural highlights

Function

Publication Abstract from PubMed

See Also

References

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