Mechanism of Action of Flavin-Dependent Halogenases.
Journal
ACS catalysis
ISSN: 2155-5435
Titre abrégé: ACS Catal
Pays: United States
ID NLM: 101562209
Informations de publication
Date de publication:
16 Dec 2022
16 Dec 2022
Historique:
received:
23
10
2022
revised:
12
11
2022
entrez:
26
12
2022
pubmed:
27
12
2022
medline:
27
12
2022
Statut:
ppublish
Résumé
To rationally engineer the substrate scope and selectivity of flavin-dependent halogenases (FDHs), it is essential to first understand the reaction mechanism and substrate interactions in the active site. FDHs have long been known to achieve regioselectivity through an electrophilic aromatic substitution at C7 of the natural substrate Trp, but the precise role of a key active-site Lys residue remains ambiguous. Formation of hypochlorous acid (HOCl) at the cofactor-binding site is achieved by the direct reaction of molecular oxygen and a single chloride ion with reduced FAD and flavin hydroxide, respectively. HOCl is then guided 10 Å into the halogenation active site. Lys79, located in this site, has been proposed to direct HOCl toward Trp C7 through hydrogen bonding or a direct reaction with HOCl to form an -NH
Identifiants
pubmed: 36570077
doi: 10.1021/acscatal.2c05231
pmc: PMC9764358
doi:
Types de publication
Journal Article
Langues
eng
Pagination
15352-15360Informations de copyright
© 2022 The Authors. Published by American Chemical Society.
Déclaration de conflit d'intérêts
The authors declare no competing financial interest.
Références
J Comput Chem. 2004 Jul 15;25(9):1157-74
pubmed: 15116359
Chembiochem. 2014 Jun 16;15(9):1286-9
pubmed: 24849696
Theochem. 2000 Aug;527(1-3):149-156
pubmed: 25309012
J Chem Phys. 2010 Apr 21;132(15):154104
pubmed: 20423165
Proc Natl Acad Sci U S A. 2005 Mar 15;102(11):3960-5
pubmed: 15743914
Chemistry. 2002 Aug 16;8(16):3580-5
pubmed: 12203284
Proteins. 2008 Jan 1;70(1):289-93
pubmed: 17876823
Angew Chem Int Ed Engl. 2000 Jul 3;39(13):2300-2302
pubmed: 10941070
Chem Soc Rev. 2012 Feb 21;41(4):1437-51
pubmed: 22033698
J Comput Chem. 2004 Oct;25(13):1605-12
pubmed: 15264254
Angew Chem Int Ed Engl. 2011 Mar 21;50(13):2951-3
pubmed: 21404376
Bioinformatics. 2013 Apr 1;29(7):845-54
pubmed: 23407358
Sci Rep. 2017 Dec 12;7(1):17395
pubmed: 29234124
J Biol Chem. 2021 Jan-Jun;296:100068
pubmed: 33465708
J Am Chem Soc. 2017 Aug 30;139(34):12060-12068
pubmed: 28777910
Biochemistry. 2007 Feb 6;46(5):1284-92
pubmed: 17260957
Chem Rev. 2014 Feb 26;114(4):2432-506
pubmed: 24299176
Beilstein J Org Chem. 2013 Oct 30;9:2265-319
pubmed: 24204439
Science. 2005 Sep 30;309(5744):2216-9
pubmed: 16195462
Biochem J. 1954 Aug;57(4):587-95
pubmed: 13198807
Microb Biotechnol. 2017 Mar;10(2):250-263
pubmed: 27145540
Nat Protoc. 2007;2(12):3247-56
pubmed: 18079725
Acc Chem Res. 2001 Dec;34(12):938-45
pubmed: 11747411
Nature. 1960 Jul 16;187:236-7
pubmed: 14438509
ACS Omega. 2018 May 02;3(5):4847-4859
pubmed: 31458701
Nature. 2011 Dec 21;480(7378):471-9
pubmed: 22193101
Angew Chem Int Ed Engl. 2008;47(49):9533-6
pubmed: 18979475
Protein Sci. 2019 Dec;28(12):2112-2118
pubmed: 31589794
J Mol Biol. 2009 Aug 7;391(1):74-85
pubmed: 19501593
Biochemistry. 2006 Jun 27;45(25):7904-12
pubmed: 16784243
Curr Opin Chem Biol. 2017 Apr;37:56-62
pubmed: 28152442
Nature. 2013 Apr 25;496(7446):528-32
pubmed: 23575629
J Chem Theory Comput. 2011 Feb 8;7(2):525-37
pubmed: 26596171