ARMH5_ARMME
ID ARMH5_ARMME Reviewed; 523 AA.
AC A0A0U3C228;
DT 20-DEC-2017, integrated into UniProtKB/Swiss-Prot.
DT 16-MAR-2016, sequence version 1.
DT 03-AUG-2022, entry version 18.
DE RecName: Full=Flavin-dependent halogenase armH5 {ECO:0000303|PubMed:26655762};
DE EC=1.14.19.- {ECO:0000269|PubMed:26655762};
GN Name=armH5 {ECO:0000303|PubMed:26655762};
OS Armillaria mellea (Shoestring root rot fungus) (Honey mushroom).
OC Eukaryota; Fungi; Dikarya; Basidiomycota; Agaricomycotina; Agaricomycetes;
OC Agaricomycetidae; Agaricales; Physalacriaceae; Armillaria.
OX NCBI_TaxID=47429;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, AND CATALYTIC ACTIVITY.
RC STRAIN=DSM 3731;
RX PubMed=26655762; DOI=10.1128/aem.03168-15;
RA Wick J., Heine D., Lackner G., Misiek M., Tauber J., Jagusch H.,
RA Hertweck C., Hoffmeister D.;
RT "A fivefold parallelized biosynthetic process secures chlorination of
RT Armillaria mellea (honey mushroom) toxins.";
RL Appl. Environ. Microbiol. 82:1196-1204(2015).
RN [2]
RP BIOTECHNOLOGY.
RX PubMed=21376582; DOI=10.1016/j.bmcl.2011.02.026;
RA Bohnert M., Miethbauer S., Dahse H.M., Ziemen J., Nett M., Hoffmeister D.;
RT "In vitro cytotoxicity of melleolide antibiotics: structural and
RT mechanistic aspects.";
RL Bioorg. Med. Chem. Lett. 21:2003-2006(2011).
RN [3]
RP BIOTECHNOLOGY.
RX PubMed=23864890; DOI=10.1155/2013/459271;
RA Chi C.W., Chen C.C., Chen Y.J.;
RT "Therapeutic and radiosensitizing effects of armillaridin on human
RT esophageal cancer cells.";
RL Evid. Based Complement Alternat. Med. 2013:459271-459271(2013).
RN [4]
RP BIOTECHNOLOGY.
RX PubMed=25746621; DOI=10.1615/intjmedmushrooms.v17.i2.70;
RA Liu T.P., Chen C.C., Shiao P.Y., Shieh H.R., Chen Y.Y., Chen Y.J.;
RT "Armillaridin, a honey medicinal mushroom, Armillaria mellea (higher
RT basidiomycetes) component, inhibits differentiation and activation of human
RT macrophages.";
RL Int. J. Med. Mushrooms 17:161-168(2015).
RN [5]
RP BIOTECHNOLOGY.
RX PubMed=26952552; DOI=10.1016/j.jep.2016.02.044;
RA Li Z., Wang Y., Jiang B., Li W., Zheng L., Yang X., Bao Y., Sun L.,
RA Huang Y., Li Y.;
RT "Structure, cytotoxic activity and mechanism of protoilludane sesquiterpene
RT aryl esters from the mycelium of Armillaria mellea.";
RL J. Ethnopharmacol. 184:119-127(2016).
RN [6]
RP BIOTECHNOLOGY.
RX PubMed=27592257; DOI=10.1007/s13277-016-5208-6;
RA Chang W.H., Huang H.L., Huang W.P., Chen C.C., Chen Y.J.;
RT "Armillaridin induces autophagy-associated cell death in human chronic
RT myelogenous leukemia K562 cells.";
RL Tumor Biol. 37:14291-14300(2016).
RN [7]
RP MISCELLANEOUS.
RX PubMed=29614282; DOI=10.1016/j.cub.2018.01.026;
RA Sipos G., Anderson J.B., Nagy L.G.;
RT "Armillaria.";
RL Curr. Biol. 28:R297-R298(2018).
RN [8]
RP BIOTECHNOLOGY.
RX PubMed=31488037; DOI=10.1142/s0192415x19500708;
RA Leu Y.S., Chen Y.J., Chen C.C., Huang H.L.;
RT "Induction of autophagic death of human hepatocellular carcinoma cells by
RT armillaridin from Armillaria mellea.";
RL Am. J. Chin. Med. 47:1365-1380(2019).
RN [9]
RP MISCELLANEOUS.
RX PubMed=31746694; DOI=10.1094/pdis-06-19-1147-re;
RA Cromey M.G., Drakulic J., Beal E.J., Waghorn I.A.G., Perry J.N.,
RA Clover G.R.G.;
RT "Susceptibility of garden trees and shrubs to Armillaria root rot.";
RL Plant Dis. 104:483-492(2020).
CC -!- FUNCTION: Flavin-dependent halogenase involved in the biosynthesis of
CC melleolides, a range of antifungal and phytotoxic polyketide
CC derivatives composed of an orsellinic acid (OA) moiety esterified to
CC various sesquiterpene alcohols. The halogenase catalyzes the transfer
CC of a single chlorine atom to the melleolide backbone, resulting in a
CC 6'-chloromelleolide product. The enzyme acts on free substrate and does
CC not depend on carrier-protein-dependent acceptor molecules.
CC {ECO:0000269|PubMed:26655762}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=chloride + FADH2 + melleolide F + O2 = 6'-chloromelleolide F +
CC FAD + H(+) + 2 H2O; Xref=Rhea:RHEA:67160, ChEBI:CHEBI:15377,
CC ChEBI:CHEBI:15378, ChEBI:CHEBI:15379, ChEBI:CHEBI:17996,
CC ChEBI:CHEBI:57692, ChEBI:CHEBI:58307, ChEBI:CHEBI:167712,
CC ChEBI:CHEBI:167713; Evidence={ECO:0000269|PubMed:26655762};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:67161;
CC Evidence={ECO:0000269|PubMed:26655762};
CC -!- BIOTECHNOLOGY: Melleolide sesquiterpene aryl esters are cytotoxic
CC secondary products with anti-cancer potential (PubMed:21376582,
CC PubMed:26952552). Armillaridin shows therapeutic and radiosensitizing
CC effects on human esophageal cancer cells (PubMed:23864890).
CC Armillaridin induces autophagy-associated cell death in human chronic
CC myelogenous leukemia as well as of hepatocellular carcinoma cells
CC (PubMed:27592257, PubMed:31488037). Armillaridin can also inhibit the
CC differentiation and activation of human macrophages and thus might have
CC potential to be developed as a biological response modifier for
CC inflammatory diseases (PubMed:25746621). {ECO:0000269|PubMed:21376582,
CC ECO:0000269|PubMed:23864890, ECO:0000269|PubMed:25746621,
CC ECO:0000269|PubMed:26952552, ECO:0000269|PubMed:27592257,
CC ECO:0000269|PubMed:31488037}.
CC -!- MISCELLANEOUS: Armillaria species are both devastating forest pathogens
CC and some of the largest and oldest terrestrial organisms on Earth
CC (PubMed:31746694) (Probable). They forage for hosts and achieve immense
CC colony sizes via rhizomorphs, root-like multicellular structures of
CC clonal dispersal (Probable). {ECO:0000269|PubMed:31746694,
CC ECO:0000305|PubMed:29614282}.
CC -!- SIMILARITY: Belongs to the flavin-dependent halogenase family.
CC {ECO:0000305}.
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DR EMBL; KT819181; ALT31852.1; -; mRNA.
DR AlphaFoldDB; A0A0U3C228; -.
DR SMR; A0A0U3C228; -.
DR GO; GO:0071949; F:FAD binding; IEA:InterPro.
DR GO; GO:0004497; F:monooxygenase activity; IEA:UniProtKB-KW.
DR Gene3D; 3.50.50.60; -; 1.
DR InterPro; IPR002938; FAD-bd.
DR InterPro; IPR036188; FAD/NAD-bd_sf.
DR Pfam; PF01494; FAD_binding_3; 1.
DR SUPFAM; SSF51905; SSF51905; 1.
PE 1: Evidence at protein level;
KW FAD; Flavoprotein; Monooxygenase; Oxidoreductase.
FT CHAIN 1..523
FT /note="Flavin-dependent halogenase armH5"
FT /id="PRO_0000442634"
FT BINDING 17..20
FT /ligand="FAD"
FT /ligand_id="ChEBI:CHEBI:57692"
FT /evidence="ECO:0000250|UniProtKB:P95480"
FT BINDING 40..51
FT /ligand="FAD"
FT /ligand_id="ChEBI:CHEBI:57692"
FT /evidence="ECO:0000250|UniProtKB:P95480"
FT BINDING 328..329
FT /ligand="chloride"
FT /ligand_id="ChEBI:CHEBI:17996"
FT /evidence="ECO:0000250|UniProtKB:P95480"
SQ SEQUENCE 523 AA; 57877 MW; E3286E0C3FF35AE2 CRC64;
MPSEYVPEAT TVLVIGGGPA GSYASTLLAR EGIDVVLLEA VKHPREHVGE SMLPSMRHYL
RFIDLESEYD ARKFMHKPGA AFKFVHGQRE CYTDFKILGP DRTTWNVFRA EADELMLRHA
ASQGVKIFEE TRVESITFSE SVDNSVSPES RPIAASWKNK SGQVGKISFN WLIDASGRQG
IMSTKYMKNR IYREGLRNVA AYGYWKDVTV FEEGGPRSNA PWFECLTDRE GWAWLIPLHN
GTTSIGVVMH QDTSNRKKAE GPSGLEQHYL SQLKLAPGVQ DLIGSKGSYV PGSVKSTADY
SYHATEYSGD HYRIIGDAAA FVDPLFSSGV HVAMTGALSA ASTILGSMKG QVTEVEAQAW
HDAKIGICQT RFLLVVLSAY RQMQHVGNKA LLDDVNASNF DAAFSLFRPI YQGEHDTSTS
LTNEELSKMI EFTRNLFTPT THQQYNEVKQ RVGDLIALSG PVMPSDELDK VLDSDDSDAK
AVLKRINSLK VLRNDTSPES FTSEAVNGYV VNLERGQLGL VRA
