HTYD_ASPRU
ID HTYD_ASPRU Reviewed; 878 AA.
AC K0E2G4;
DT 25-APR-2018, integrated into UniProtKB/Swiss-Prot.
DT 28-NOV-2012, sequence version 1.
DT 03-AUG-2022, entry version 29.
DE RecName: Full=Aconitase htyD {ECO:0000303|PubMed:22998630};
DE EC=4.2.1.- {ECO:0000305|PubMed:22998630};
DE AltName: Full=L-homotyrosine biosynthetic cluster protein D {ECO:0000303|PubMed:22998630};
GN Name=htyD {ECO:0000303|PubMed:22998630};
OS Aspergillus rugulosus (Emericella rugulosa).
OC Eukaryota; Fungi; Dikarya; Ascomycota; Pezizomycotina; Eurotiomycetes;
OC Eurotiomycetidae; Eurotiales; Aspergillaceae; Aspergillus.
OX NCBI_TaxID=41736;
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], FUNCTION, PATHWAY, AND BIOTECHNOLOGY.
RC STRAIN=ATCC 58397 / NRRL 11440;
RX PubMed=22998630; DOI=10.1021/ja307220z;
RA Cacho R.A., Jiang W., Chooi Y.H., Walsh C.T., Tang Y.;
RT "Identification and characterization of the echinocandin B biosynthetic
RT gene cluster from Emericella rugulosa NRRL 11440.";
RL J. Am. Chem. Soc. 134:16781-16790(2012).
CC -!- FUNCTION: Aconitase; part of the gene cluster that mediates the de novo
CC generation of L-homotyrosine from acetyl-CoA and 4-hydroxyphenyl-
CC pyruvate (PubMed:22998630). L-homotyrosine is a building block of
CC echinocandin B, a fungal lipidated cyclic hexapeptide that acts as an
CC antifungal agent (PubMed:22998630). L-homotyrosine 4-hydroxyphenyl-
CC pyruvate first undergoes an aldol-type condensation by htyA with the C-
CC 2 of acetyl-CoA followed by the release of CoA to form 2-(4-
CC hydroxybenzyl)-malate (PubMed:22998630). This is followed by
CC isomerization of 2-(4-hydroxy-benzyl)-malate to 3-(4-hydroxybenzyl)-
CC malate by htyD (PubMed:22998630). Thereafter, 3-(4-hydroxybenzyl)-
CC malate undergoes decarboxylation and oxidation to form 2-oxo-4-(4-
CC hydroxybenzyl)butanoic acid, coupled to reduction of NAD(+) to NADH by
CC htyC (PubMed:22998630). The product then undergoes transamination
CC catalyzed by htyB to form L-homotyrosine (PubMed:22998630).
CC {ECO:0000269|PubMed:22998630}.
CC -!- PATHWAY: Antifungal biosynthesis. {ECO:0000305|PubMed:22998630}.
CC -!- BIOTECHNOLOGY: Due to their effectiveness as antifungal agents,
CC echinocandin derivatives can be used for the treatment of human
CC invasive candidiasis (PubMed:22998630). {ECO:0000269|PubMed:22998630}.
CC -!- SIMILARITY: Belongs to the aconitase/IPM isomerase family.
CC {ECO:0000305}.
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DR EMBL; JX421685; AFT91395.1; -; Genomic_DNA.
DR AlphaFoldDB; K0E2G4; -.
DR SMR; K0E2G4; -.
DR BioCyc; MetaCyc:MON-19235; -.
DR GO; GO:0051536; F:iron-sulfur cluster binding; IEA:UniProtKB-KW.
DR GO; GO:0016829; F:lyase activity; IEA:UniProtKB-KW.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR CDD; cd01577; IPMI_Swivel; 1.
DR Gene3D; 3.20.19.10; -; 1.
DR Gene3D; 3.30.499.10; -; 2.
DR InterPro; IPR015931; Acnase/IPM_dHydase_lsu_aba_1/3.
DR InterPro; IPR001030; Acoase/IPM_deHydtase_lsu_aba.
DR InterPro; IPR015928; Aconitase/3IPM_dehydase_swvl.
DR InterPro; IPR018136; Aconitase_4Fe-4S_BS.
DR InterPro; IPR036008; Aconitase_4Fe-4S_dom.
DR InterPro; IPR000573; AconitaseA/IPMdHydase_ssu_swvl.
DR InterPro; IPR033940; IPMI_Swivel.
DR Pfam; PF00330; Aconitase; 1.
DR Pfam; PF00694; Aconitase_C; 1.
DR PRINTS; PR00415; ACONITASE.
DR SUPFAM; SSF53732; SSF53732; 1.
DR PROSITE; PS01244; ACONITASE_2; 1.
PE 1: Evidence at protein level;
KW Iron; Iron-sulfur; Lyase; Metal-binding.
FT CHAIN 1..878
FT /note="Aconitase htyD"
FT /id="PRO_0000443854"
FT REGION 626..671
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT BINDING 173
FT /ligand="substrate"
FT /evidence="ECO:0000250|UniProtKB:P20004"
FT BINDING 290..292
FT /ligand="substrate"
FT /evidence="ECO:0000250|UniProtKB:P20004"
FT BINDING 472
FT /ligand="[4Fe-4S] cluster"
FT /ligand_id="ChEBI:CHEBI:49883"
FT /evidence="ECO:0000250|UniProtKB:P20004"
FT BINDING 535
FT /ligand="[4Fe-4S] cluster"
FT /ligand_id="ChEBI:CHEBI:49883"
FT /evidence="ECO:0000250|UniProtKB:P20004"
FT BINDING 538
FT /ligand="[4Fe-4S] cluster"
FT /ligand_id="ChEBI:CHEBI:49883"
FT /evidence="ECO:0000250|UniProtKB:P20004"
FT BINDING 558
FT /ligand="substrate"
FT /evidence="ECO:0000250|UniProtKB:P20004"
FT BINDING 563
FT /ligand="substrate"
FT /evidence="ECO:0000250|UniProtKB:P20004"
FT BINDING 742..743
FT /ligand="substrate"
FT /evidence="ECO:0000250|UniProtKB:P20004"
SQ SEQUENCE 878 AA; 95013 MW; A19A80588062DBE6 CRC64;
MSEGSISLCF LGSLPNDVVN FVRAVVRILA DIRGIVVEER SAEELSLSNP PTLTLAALDN
TEPGSPAICS LYAFLTHLCT ALETIGRHAE VSSLQHVLDL CRTTTDRGGL AIIRDESSGW
TSGPTQLQSV QSLIEAWLEA LNAAESATQL PAPLPAKTPN TWPMTLAEKI LVQHAFSLPS
PQGVSVGELM RVSVDWVIAS ELSWVGMKHS MISIGEQPTV WRNDRFWLAG DHTVDPRTYH
QPRVQELIGG MEDAKKTFKM TENQGSNYTI LHTEFVRERA EPGMLVIGSD SHTCSAGAVS
SLAIGLGAAD VMAALATGET WFKSPESIRV EFSGEPAWYI RGKDIILYIL KKLKRNTHAA
DRIVEFGGPG AKHLSCDARF AICNMCTELG AITGIFVPDE VTHQFISNRR HSRYRSNSVY
FQPDSDASYA ATFQIDLSEV ESFIALYPSP DNVVPVTETL DMPLDGCFIG ACTTTEEDLV
LAALVLEVGL QQGLELAIGK RMVVPGSLPI VSNLRVLGLL DVFEQAGFEQ PAVSCSLCLG
MGADRAGHGE NWLSSQNRNF KNRMGHGSIG HICSAAVVAA SSFSMRVTDP RPLLSQIPPE
RYQTLLDKCR DWRSAEPAAR RHPGKIAIAN QRTKPAPTMP AYVEPYRSFQ PPVPPSSDQP
QSMKDHGKTS NGENGILISK VYALGDFVDT DAIIPAAFIL ESPTDVLLGS HCLEFTNPDF
RSQVRAGLEV VVAGKAFGCG SSREEAPRAL KGLGVKCVIA KSFSFIYGRN QPTIGLLGIV
ITDERFYDAA RTGVAIEINP SARTVTVAGQ SFPFVMDDME LALIRRDGLA TAYKALGKGV
FRSLCADVPG KGGCGQTQGT IYMQVSMSLR VTPAVSRD
