4dnj: Difference between revisions
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The | ==The crystal structures of 4-methoxybenzoate bound CYP199A2== | ||
<StructureSection load='4dnj' size='340' side='right'caption='[[4dnj]], [[Resolution|resolution]] 1.80Å' scene=''> | |||
== Structural highlights == | |||
<table><tr><td colspan='2'>[[4dnj]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Rhodopseudomonas_palustris_CGA009 Rhodopseudomonas palustris CGA009]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4DNJ OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4DNJ 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]] 1.8Å</td></tr> | |||
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=ANN:4-METHOXYBENZOIC+ACID'>ANN</scene>, <scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=HEM:PROTOPORPHYRIN+IX+CONTAINING+FE'>HEM</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=4dnj FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4dnj OCA], [https://pdbe.org/4dnj PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4dnj RCSB], [https://www.ebi.ac.uk/pdbsum/4dnj PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4dnj ProSAT]</span></td></tr> | |||
</table> | |||
== Function == | |||
[https://www.uniprot.org/uniprot/CYPA2_RHOPA CYPA2_RHOPA] The oxidative demethylation of 4-methoxybenzoate requires the participation of the monooxygenase CYP199A2, the ferredoxin-like protein ThcC/RPA1872 and a ferredoxin reductase to mediate the transfer of electrons from NADH to CYP199A2. It is also active with 4-ethylbenzoate.<ref>PMID:16472768</ref> <ref>PMID:18762195</ref> | |||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
The crystal structures of the 4-methoxybenzoate bound forms of cytochrome P450 enzymes CYP199A2 and CYP199A4 from the Rhodopseudomonas palustris strains CGA009 and HaA2 have been solved. The structures of these two enzymes, which share 86% sequence identity, are very similar though some differences are found on the proximal surface. In these structures the enzymes have a closed conformation, in contrast to the substrate-free form of CYP199A2 where an obvious substrate access channel is observed. The switch from an open to a closed conformation arises from pronounced residue side-chain movements and alterations of ion pair and hydrogen bonding interactions at the entrance of the access channel. A chloride ion bound just inside the protein surface caps the entrance to the active site and protects the substrate and the heme from the external solvent. In both structures the substrate is held in place via hydrophobic and hydrogen bond interactions. The methoxy group is located over the heme iron, accounting for the high activity and selectivity of these enzymes for oxidative demethylation of the substrate. Mutagenesis studies on CYP199A4 highlight the involvement of hydrophobic (Phe185) and hydrophilic (Arg92, Ser95 and Arg243) amino acid residues in the binding of para-substituted benzoates by these enzymes. | |||
The crystal structures of 4-methoxybenzoate bound CYP199A2 and CYP199A4: structural changes on substrate binding and the identification of an anion binding site.,Bell SG, Yang W, Tan AB, Zhou R, Johnson EO, Zhang A, Zhou W, Rao Z, Wong LL Dalton Trans. 2012 Jul 28;41(28):8703-14. Epub 2012 Jun 13. PMID:22695988<ref>PMID:22695988</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
</div> | |||
<div class="pdbe-citations 4dnj" style="background-color:#fffaf0;"></div> | |||
== References == | |||
<references/> | |||
__TOC__ | |||
</StructureSection> | |||
[[Category: Large Structures]] | |||
[[Category: Rhodopseudomonas palustris CGA009]] | |||
[[Category: Bell SG]] | |||
[[Category: Johnson EOD]] | |||
[[Category: Rao Z]] | |||
[[Category: Tan ABH]] | |||
[[Category: Wong L-L]] | |||
[[Category: Yang W]] | |||
[[Category: Zhang A]] | |||
[[Category: Zhou R]] | |||
[[Category: Zhou W]] | |||
Latest revision as of 16:43, 8 November 2023
The crystal structures of 4-methoxybenzoate bound CYP199A2The crystal structures of 4-methoxybenzoate bound CYP199A2
Structural highlights
FunctionCYPA2_RHOPA The oxidative demethylation of 4-methoxybenzoate requires the participation of the monooxygenase CYP199A2, the ferredoxin-like protein ThcC/RPA1872 and a ferredoxin reductase to mediate the transfer of electrons from NADH to CYP199A2. It is also active with 4-ethylbenzoate.[1] [2] Publication Abstract from PubMedThe crystal structures of the 4-methoxybenzoate bound forms of cytochrome P450 enzymes CYP199A2 and CYP199A4 from the Rhodopseudomonas palustris strains CGA009 and HaA2 have been solved. The structures of these two enzymes, which share 86% sequence identity, are very similar though some differences are found on the proximal surface. In these structures the enzymes have a closed conformation, in contrast to the substrate-free form of CYP199A2 where an obvious substrate access channel is observed. The switch from an open to a closed conformation arises from pronounced residue side-chain movements and alterations of ion pair and hydrogen bonding interactions at the entrance of the access channel. A chloride ion bound just inside the protein surface caps the entrance to the active site and protects the substrate and the heme from the external solvent. In both structures the substrate is held in place via hydrophobic and hydrogen bond interactions. The methoxy group is located over the heme iron, accounting for the high activity and selectivity of these enzymes for oxidative demethylation of the substrate. Mutagenesis studies on CYP199A4 highlight the involvement of hydrophobic (Phe185) and hydrophilic (Arg92, Ser95 and Arg243) amino acid residues in the binding of para-substituted benzoates by these enzymes. The crystal structures of 4-methoxybenzoate bound CYP199A2 and CYP199A4: structural changes on substrate binding and the identification of an anion binding site.,Bell SG, Yang W, Tan AB, Zhou R, Johnson EO, Zhang A, Zhou W, Rao Z, Wong LL Dalton Trans. 2012 Jul 28;41(28):8703-14. Epub 2012 Jun 13. PMID:22695988[3] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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