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RADH_FLOCH
ID   RADH_FLOCH              Reviewed;         520 AA.
AC   C5H881;
DT   31-JAN-2018, integrated into UniProtKB/Swiss-Prot.
DT   28-JUL-2009, sequence version 1.
DT   03-AUG-2022, entry version 26.
DE   RecName: Full=Non-heme halogenase radH {ECO:0000303|PubMed:19101477};
DE            EC=1.14.14.- {ECO:0000305|PubMed:19101477};
DE   AltName: Full=Radicicol biosynthesis cluster protein radH {ECO:0000303|PubMed:19101477};
GN   Name=radH {ECO:0000303|PubMed:19101477};
OS   Floropilus chiversii (Chaetomium chiversii).
OC   Eukaryota; Fungi; Dikarya; Ascomycota; Pezizomycotina; Sordariomycetes;
OC   Sordariomycetidae; Sordariales; Chaetomiaceae; Floropilus.
OX   NCBI_TaxID=2587399;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [GENOMIC DNA], FUNCTION, AND DISRUPTION PHENOTYPE.
RC   STRAIN=CS-36-62;
RX   PubMed=19101477; DOI=10.1016/j.chembiol.2008.10.006;
RA   Wang S., Xu Y., Maine E.A., Wijeratne E.M., Espinosa-Artiles P.,
RA   Gunatilaka A.A., Molnar I.;
RT   "Functional characterization of the biosynthesis of radicicol, an Hsp90
RT   inhibitor resorcylic acid lactone from Chaetomium chiversii.";
RL   Chem. Biol. 15:1328-1338(2008).
CC   -!- FUNCTION: Non-heme halogenase; part of the gene cluster that mediates
CC       the biosynthesis of radicicol, a resorcylic acid lactone (RAL) that
CC       irreversibly inhibits the HSP90 molecular chaperone, an important
CC       target for cancer chemotherapy (PubMed:19101477). The cluster encodes
CC       only two apparent post-PKS enzymes, a cytochrome P450 monooxygenase
CC       (radP) and a non-heme halogenase (radH) that introduce the epoxide and
CC       the chlorine, respectively (PubMed:19101477). If this cluster includes
CC       all the genes required for radicicol biosynthesis, the remaining
CC       structural features of radicicol are presumably generated by the PKSs
CC       rads1 and rads2 (PubMed:19101477). The C-2' ketone could arise if the
CC       R-PKS rads1 and NR-PKS rads2 each carry out four iterations, in
CC       contrast to the five iteration-three iteration split for the
CC       hypothemycin PKSs (By similarity). The origin of the cis 5',6' double
CC       bond is not known (By similarity). The radicicol R-PKS rads1 ER domain
CC       may catalyze either double bond isomerization or reduction in the third
CC       iteration (By similarity). {ECO:0000250|UniProtKB:B3FWT7,
CC       ECO:0000269|PubMed:19101477}.
CC   -!- COFACTOR:
CC       Name=FAD; Xref=ChEBI:CHEBI:57692;
CC         Evidence={ECO:0000250|UniProtKB:P95480};
CC       Note=Binds 1 FAD per subunit. {ECO:0000250|UniProtKB:P95480};
CC   -!- PATHWAY: Secondary metabolite biosynthesis.
CC       {ECO:0000269|PubMed:19101477}.
CC   -!- DISRUPTION PHENOTYPE: Abolishes the production of radicicol and
CC       accumulates 6-dechloro-radicicol, also known as monocillin I
CC       (PubMed:19101477). {ECO:0000269|PubMed:19101477}.
CC   -!- BIOTECHNOLOGY: Radicicol is an important pharmacophore as an inhibitor
CC       of heat shock protein 90 (Hsp90), an ATP-dependent chaperone involved
CC       in the post-translational maturation and stabilization of over one
CC       hundred proteins, and which activity has been implicated in diverse
CC       pathologies ranging from oncology to neurodegenerative and infectious
CC       diseases (PubMed:19101477). {ECO:0000305|PubMed:19101477}.
CC   -!- SIMILARITY: Belongs to the flavin-dependent halogenase family.
CC       {ECO:0000305}.
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DR   EMBL; EU980390; ACM42402.1; -; Genomic_DNA.
DR   AlphaFoldDB; C5H881; -.
DR   SMR; C5H881; -.
DR   GO; GO:0004497; F:monooxygenase activity; IEA:UniProtKB-KW.
DR   Gene3D; 3.50.50.60; -; 1.
DR   InterPro; IPR036188; FAD/NAD-bd_sf.
DR   InterPro; IPR006905; Flavin_halogenase.
DR   Pfam; PF04820; Trp_halogenase; 2.
DR   SUPFAM; SSF51905; SSF51905; 1.
PE   3: Inferred from homology;
KW   FAD; Flavoprotein; Monooxygenase; Oxidoreductase.
FT   CHAIN           1..520
FT                   /note="Non-heme halogenase radH"
FT                   /id="PRO_0000443045"
FT   BINDING         14..17
FT                   /ligand="FAD"
FT                   /ligand_id="ChEBI:CHEBI:57692"
FT                   /evidence="ECO:0000250|UniProtKB:P95480"
FT   BINDING         37..48
FT                   /ligand="FAD"
FT                   /ligand_id="ChEBI:CHEBI:57692"
FT                   /evidence="ECO:0000250|UniProtKB:P95480"
FT   BINDING         330..331
FT                   /ligand="chloride"
FT                   /ligand_id="ChEBI:CHEBI:17996"
FT                   /evidence="ECO:0000250|UniProtKB:P95480"
SQ   SEQUENCE   520 AA;  56453 MW;  420793B520132F47 CRC64;
     MSIPKSCEVL VAGGGPAGSY AASALAREGV DVVLLEADKH PRYHIGESML PSIRPLLRFI
     DLEETFEKHG FQKKLGAAFK LTAKREGYTD FVAAHGPNGY SWNVVRSESD ELLFKHAAKS
     GALTFQGVKV DSLEFEPYDS DFPSGGKVAN PGRPVAARWS AKDGRSGTIS FQYLVDATGR
     AGITSTKYLK NRKFNEGLKN LAIWGYYKGA RPWAEGTPRE NQPYFEGMRD GAGWCWTIPL
     HNGTVSVGAV LRSDLFFAKK KSLGEDVTNA MIMAECMKLC PTIKELLEPA ELVSDIKQAT
     DYSYSASAYA GPYFRIVGDA GCFIDPFFSS GHHLAMAGAL AAAVSIRASM KGDCSEYEAS
     NWHARKVDEG YTLFLLVVMA ALKQIRMQEE PVLSDIDDDG FDRAFQFLKP VIQGSGSAEI
     VKRFTKKEVS EAIDFAVLAL DNMAGAGEHA NETNGSNGTG ETNGDAKTLE NITVEDEKVL
     SGIRILAKVA PSADMKDLEG TAIDGFMPRL EHGHLGLNRV
 
 
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