7ydc: Difference between revisions
No edit summary |
No edit summary |
||
| Line 1: | Line 1: | ||
==Crystal structure of the P450 BM3 heme domain mutant F87L/T268V/V78C in complex with N-imidazolyl-pentanoyl-L-phenylalanine and hydroxylamine== | |||
<StructureSection load='7ydc' size='340' side='right'caption='[[7ydc]], [[Resolution|resolution]] 1.61Å' scene=''> | |||
== Structural highlights == | |||
<table><tr><td colspan='2'>[[7ydc]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Priestia_megaterium_NBRC_15308_=_ATCC_14581 Priestia megaterium NBRC 15308 = ATCC 14581]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7YDC OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7YDC FirstGlance]. <br> | |||
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=HEM:PROTOPORPHYRIN+IX+CONTAINING+FE'>HEM</scene>, <scene name='pdbligand=HOA:HYDROXYAMINE'>HOA</scene>, <scene name='pdbligand=IRV:(2~{S})-2-(5-imidazol-1-ylpentanoylamino)-3-phenyl-propanoic+acid'>IRV</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=7ydc FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7ydc OCA], [https://pdbe.org/7ydc PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7ydc RCSB], [https://www.ebi.ac.uk/pdbsum/7ydc PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7ydc ProSAT]</span></td></tr> | |||
</table> | |||
== Function == | |||
[https://www.uniprot.org/uniprot/CPXB_PRIM2 CPXB_PRIM2] Functions as a fatty acid monooxygenase (PubMed:3106359, PubMed:1727637, PubMed:16566047, PubMed:7578081, PubMed:11695892, PubMed:14653735, PubMed:16403573, PubMed:18004886, PubMed:17077084, PubMed:17868686, PubMed:18298086, PubMed:18619466, PubMed:18721129, PubMed:19492389, PubMed:20180779, PubMed:21110374, PubMed:21875028). Catalyzes hydroxylation of fatty acids at omega-1, omega-2 and omega-3 positions (PubMed:1727637, PubMed:21875028). Shows activity toward medium and long-chain fatty acids, with optimum chain lengths of 12, 14 and 16 carbons (lauric, myristic, and palmitic acids). Able to metabolize some of these primary metabolites to secondary and tertiary products (PubMed:1727637). Marginal activity towards short chain lengths of 8-10 carbons (PubMed:1727637, PubMed:18619466). Hydroxylates highly branched fatty acids, which play an essential role in membrane fluidity regulation (PubMed:16566047). Also displays a NADPH-dependent reductase activity in the C-terminal domain, which allows electron transfer from NADPH to the heme iron of the cytochrome P450 N-terminal domain (PubMed:3106359, PubMed:1727637, PubMed:16566047, PubMed:7578081, PubMed:11695892, PubMed:14653735, PubMed:16403573, PubMed:18004886, PubMed:17077084, PubMed:17868686, PubMed:18298086, PubMed:18619466, PubMed:18721129, PubMed:19492389, PubMed:20180779, PubMed:21110374, PubMed:21875028). Involved in inactivation of quorum sensing signals of other competing bacteria by oxidazing efficiently acyl homoserine lactones (AHLs), molecules involved in quorum sensing signaling pathways, and their lactonolysis products acyl homoserines (AHs) (PubMed:18020460).<ref>PMID:11695892</ref> <ref>PMID:14653735</ref> <ref>PMID:16403573</ref> <ref>PMID:16566047</ref> <ref>PMID:17077084</ref> <ref>PMID:1727637</ref> <ref>PMID:17868686</ref> <ref>PMID:18004886</ref> <ref>PMID:18020460</ref> <ref>PMID:18298086</ref> <ref>PMID:18619466</ref> <ref>PMID:18721129</ref> <ref>PMID:19492389</ref> <ref>PMID:20180779</ref> <ref>PMID:21110374</ref> <ref>PMID:21875028</ref> <ref>PMID:3106359</ref> <ref>PMID:7578081</ref> | |||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
It is a great challenge to optionally access diverse hydroxylation products from a given substrate bearing multiple reaction sites of sp(3) and sp(2) C-H bonds. Herein, we report the highly selective divergent hydroxylation of alkylbenzenes by an engineered P450 peroxygenase driven by a dual-functional small molecule (DFSM). Using combinations of various P450BM3 variants with DFSMs enabled access to more than half of all possible hydroxylated products from each substrate with excellent regioselectivity (up to >99 %), enantioselectivity (up to >99 % ee), and high total turnover numbers (up to 80963). Crystal structure analysis, molecular dynamic simulations, and theoretical calculations revealed that synergistic effects between exogenous DFSMs and the protein environment controlled regio- and enantioselectivity. This work has implications for exogenous-molecule-modulated enzymatic regiodivergent and enantioselective hydroxylation with potential applications in synthetic chemistry. | |||
Regiodivergent and Enantioselective Hydroxylation of C-H bonds by Synergistic Use of Protein Engineering and Exogenous Dual-Functional Small Molecules.,Chen J, Dong S, Fang W, Jiang Y, Chen Z, Qin X, Wang C, Zhou H, Jin L, Feng Y, Wang B, Cong Z Angew Chem Int Ed Engl. 2023 Jan 23;62(4):e202215088. doi: , 10.1002/anie.202215088. Epub 2022 Dec 14. PMID:36417593<ref>PMID:36417593</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
[[Category: | </div> | ||
[[Category: | <div class="pdbe-citations 7ydc" style="background-color:#fffaf0;"></div> | ||
[[Category: | == References == | ||
[[Category: | <references/> | ||
[[Category: Feng | __TOC__ | ||
[[Category: Jiang | </StructureSection> | ||
[[Category: Large Structures]] | |||
[[Category: Priestia megaterium NBRC 15308 = ATCC 14581]] | |||
[[Category: Chen J]] | |||
[[Category: Cong Z]] | |||
[[Category: Dong S]] | |||
[[Category: Feng Y]] | |||
[[Category: Jiang Y]] | |||