4wpz: Difference between revisions
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==Crystal structure of cytochrome P450 CYP107W1 from Streptomyces avermitilis== | |||
<StructureSection load='4wpz' size='340' side='right'caption='[[4wpz]], [[Resolution|resolution]] 2.10Å' scene=''> | |||
== Structural highlights == | |||
<table><tr><td colspan='2'>[[4wpz]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Streptomyces_avermitilis Streptomyces avermitilis]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4WPZ OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4WPZ 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]] 2.1Å</td></tr> | |||
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CSD:3-SULFINOALANINE'>CSD</scene>, <scene name='pdbligand=HEM:PROTOPORPHYRIN+IX+CONTAINING+FE'>HEM</scene>, <scene name='pdbligand=K:POTASSIUM+ION'>K</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=4wpz FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4wpz OCA], [https://pdbe.org/4wpz PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4wpz RCSB], [https://www.ebi.ac.uk/pdbsum/4wpz PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4wpz ProSAT]</span></td></tr> | |||
</table> | |||
== Function == | |||
[https://www.uniprot.org/uniprot/Q93HJ0_STRAX Q93HJ0_STRAX] | |||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
Streptomyces avermitilis contains 33 cytochrome P450 genes in its genome, many of which play important roles in the biosynthesis process of antimicrobial agents. Here, we characterized the biochemical function and structure of CYP107W1 from S. avermitilis, which is responsible for the 12-hydroxylation reaction of oligomycin C. CYP107W1 was expressed and purified from Escherichia coli. Purified proteins exhibited the typical CO-binding spectrum of P450. Interaction of oligomycin C and oligomycin A (12-hydroxylated oligomycin C) with purified CYP107W1 resulted in a type I binding with Kd values of 14.4+/-0.7muM and 2.0+/-0.1muM, respectively. LC-mass spectrometry analysis showed that CYP107W1 produced oligomycin A by regioselectively hydroxylating C12 of oligomycin C. Steady-state kinetic analysis yielded a kcat value of 0.2min-1 and a Km value of 18muM. The crystal structure of CYP107W1 was determined at 2.1A resolution. The overall P450 folding conformations are well conserved, and the open access binding pocket for the large macrolide oligomycin C was observed above the distal side of heme. This study of CYP107W1 can help a better understanding of clinically important P450 enzymes as well as their optimization and engineering for synthesizing novel antibacterial agents and other pharmaceutically important compounds. | |||
Functional characterization of CYP107W1 from Streptomyces avermitilis and biosynthesis of macrolide oligomycin A.,Han S, Pham TV, Kim JH, Lim YR, Park HG, Cha GS, Yun CH, Chun YJ, Kang LW, Kim D Arch Biochem Biophys. 2015 Apr 4;575:1-7. doi: 10.1016/j.abb.2015.03.025. PMID:25849761<ref>PMID:25849761</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
</div> | |||
<div class="pdbe-citations 4wpz" style="background-color:#fffaf0;"></div> | |||
==See Also== | |||
*[[Cytochrome P450 3D structures|Cytochrome P450 3D structures]] | |||
== References == | |||
<references/> | |||
__TOC__ | |||
</StructureSection> | |||
[[Category: Large Structures]] | |||
[[Category: Streptomyces avermitilis]] | |||
[[Category: Han SH]] | |||
[[Category: Kang LW]] | |||
[[Category: Kim DH]] | |||
[[Category: Pham TV]] | |||
Latest revision as of 14:28, 6 November 2024
Crystal structure of cytochrome P450 CYP107W1 from Streptomyces avermitilisCrystal structure of cytochrome P450 CYP107W1 from Streptomyces avermitilis
Structural highlights
FunctionPublication Abstract from PubMedStreptomyces avermitilis contains 33 cytochrome P450 genes in its genome, many of which play important roles in the biosynthesis process of antimicrobial agents. Here, we characterized the biochemical function and structure of CYP107W1 from S. avermitilis, which is responsible for the 12-hydroxylation reaction of oligomycin C. CYP107W1 was expressed and purified from Escherichia coli. Purified proteins exhibited the typical CO-binding spectrum of P450. Interaction of oligomycin C and oligomycin A (12-hydroxylated oligomycin C) with purified CYP107W1 resulted in a type I binding with Kd values of 14.4+/-0.7muM and 2.0+/-0.1muM, respectively. LC-mass spectrometry analysis showed that CYP107W1 produced oligomycin A by regioselectively hydroxylating C12 of oligomycin C. Steady-state kinetic analysis yielded a kcat value of 0.2min-1 and a Km value of 18muM. The crystal structure of CYP107W1 was determined at 2.1A resolution. The overall P450 folding conformations are well conserved, and the open access binding pocket for the large macrolide oligomycin C was observed above the distal side of heme. This study of CYP107W1 can help a better understanding of clinically important P450 enzymes as well as their optimization and engineering for synthesizing novel antibacterial agents and other pharmaceutically important compounds. Functional characterization of CYP107W1 from Streptomyces avermitilis and biosynthesis of macrolide oligomycin A.,Han S, Pham TV, Kim JH, Lim YR, Park HG, Cha GS, Yun CH, Chun YJ, Kang LW, Kim D Arch Biochem Biophys. 2015 Apr 4;575:1-7. doi: 10.1016/j.abb.2015.03.025. PMID:25849761[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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