DOHH_LEIDO
ID DOHH_LEIDO Reviewed; 326 AA.
AC D9IFD5;
DT 31-OCT-2012, integrated into UniProtKB/Swiss-Prot.
DT 05-OCT-2010, sequence version 1.
DT 03-AUG-2022, entry version 40.
DE RecName: Full=Deoxyhypusine hydroxylase {ECO:0000255|HAMAP-Rule:MF_03101, ECO:0000312|EMBL:ADJ39999.1};
DE Short=DOHH {ECO:0000255|HAMAP-Rule:MF_03101, ECO:0000303|PubMed:22438895};
DE EC=1.14.99.29 {ECO:0000250|UniProtKB:Q9BU89, ECO:0000255|HAMAP-Rule:MF_03101};
DE AltName: Full=Deoxyhypusine dioxygenase {ECO:0000250|UniProtKB:Q9BU89, ECO:0000255|HAMAP-Rule:MF_03101};
DE AltName: Full=Deoxyhypusine monooxygenase {ECO:0000250|UniProtKB:Q9BU89, ECO:0000255|HAMAP-Rule:MF_03101};
GN Name=DOHH {ECO:0000255|HAMAP-Rule:MF_03101, ECO:0000312|EMBL:ADJ39999.1};
OS Leishmania donovani.
OC Eukaryota; Discoba; Euglenozoa; Kinetoplastea; Metakinetoplastina;
OC Trypanosomatida; Trypanosomatidae; Leishmaniinae; Leishmania.
OX NCBI_TaxID=5661;
RN [1] {ECO:0000305, ECO:0000312|EMBL:ADJ39999.1}
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], FUNCTION, CATALYTIC ACTIVITY, COFACTOR,
RP ACTIVITY REGULATION, AND 3D-STRUCTURE MODELING.
RX PubMed=22438895; DOI=10.1371/journal.pone.0033138;
RA Chawla B., Kumar R.R., Tyagi N., Subramanian G., Srinivasan N., Park M.H.,
RA Madhubala R.;
RT "A unique modification of the eukaryotic initiation factor 5A shows the
RT presence of the complete hypusine pathway in Leishmania donovani.";
RL PLoS ONE 7:E33138-E33138(2012).
CC -!- FUNCTION: Catalyzes the hydroxylation of the N(6)-(4-aminobutyl)-L-
CC lysine intermediate produced by deoxyhypusine synthase/DHPS on a
CC critical lysine of the eukaryotic translation initiation factor 5A/eIF-
CC 5A. This is the second step of the post-translational modification of
CC that lysine into an unusual amino acid residue named hypusine.
CC Hypusination is unique to mature eIF-5A factor and is essential for its
CC function. {ECO:0000250|UniProtKB:Q99LN9, ECO:0000255|HAMAP-
CC Rule:MF_03101}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=[eIF5A protein]-deoxyhypusine + AH2 + O2 = [eIF5A protein]-
CC hypusine + A + H2O; Xref=Rhea:RHEA:14101, Rhea:RHEA-COMP:10144,
CC Rhea:RHEA-COMP:12592, ChEBI:CHEBI:13193, ChEBI:CHEBI:15377,
CC ChEBI:CHEBI:15379, ChEBI:CHEBI:17499, ChEBI:CHEBI:82657,
CC ChEBI:CHEBI:91175; EC=1.14.99.29; Evidence={ECO:0000255|HAMAP-
CC Rule:MF_03101, ECO:0000269|PubMed:22438895};
CC -!- COFACTOR:
CC Name=Fe(2+); Xref=ChEBI:CHEBI:29033;
CC Evidence={ECO:0000255|HAMAP-Rule:MF_03101,
CC ECO:0000269|PubMed:22438895, ECO:0000305};
CC Note=Binds 2 Fe(2+) ions per subunit. {ECO:0000255|HAMAP-Rule:MF_03101,
CC ECO:0000269|PubMed:22438895, ECO:0000305};
CC -!- ACTIVITY REGULATION: Inhibited by metal chelators ciclopirox olamine
CC and mimosine, both of which also significantly inhibit growth. Kojic
CC acid has no effect on activity. {ECO:0000269|PubMed:22438895}.
CC -!- PATHWAY: Protein modification; eIF5A hypusination.
CC {ECO:0000250|UniProtKB:Q9BU89, ECO:0000255|HAMAP-Rule:MF_03101}.
CC -!- SIMILARITY: Belongs to the deoxyhypusine hydroxylase family.
CC {ECO:0000255|HAMAP-Rule:MF_03101}.
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DR EMBL; HM138676; ADJ39999.1; -; Genomic_DNA.
DR RefSeq; XP_003861777.1; XM_003861729.1.
DR AlphaFoldDB; D9IFD5; -.
DR SMR; D9IFD5; -.
DR GeneID; 13389024; -.
DR KEGG; ldo:LDBPK_261920; -.
DR VEuPathDB; TriTrypDB:LdBPK_261920.1; -.
DR VEuPathDB; TriTrypDB:LdCL_260024700; -.
DR VEuPathDB; TriTrypDB:LDHU3_26.2490; -.
DR OMA; CIQILNR; -.
DR UniPathway; UPA00354; -.
DR GO; GO:0019135; F:deoxyhypusine monooxygenase activity; IEA:UniProtKB-UniRule.
DR GO; GO:0005506; F:iron ion binding; IDA:UniProtKB.
DR GO; GO:0046516; P:hypusine metabolic process; IDA:UniProtKB.
DR GO; GO:0008612; P:peptidyl-lysine modification to peptidyl-hypusine; IDA:UniProtKB.
DR Gene3D; 1.25.10.10; -; 2.
DR HAMAP; MF_03101; Deoxyhypusine_hydroxylase; 1.
DR InterPro; IPR011989; ARM-like.
DR InterPro; IPR016024; ARM-type_fold.
DR InterPro; IPR027517; Deoxyhypusine_hydroxylase.
DR InterPro; IPR021133; HEAT_type_2.
DR InterPro; IPR004155; PBS_lyase_HEAT.
DR SMART; SM00567; EZ_HEAT; 5.
DR SUPFAM; SSF48371; SSF48371; 1.
DR PROSITE; PS50077; HEAT_REPEAT; 1.
PE 1: Evidence at protein level;
KW Hypusine biosynthesis; Iron; Metal-binding; Monooxygenase; Oxidoreductase;
KW Repeat.
FT CHAIN 1..326
FT /note="Deoxyhypusine hydroxylase"
FT /id="PRO_0000419764"
FT REPEAT 62..88
FT /note="HEAT-like PBS-type 1"
FT /evidence="ECO:0000255"
FT REPEAT 95..124
FT /note="HEAT-like PBS-type 2"
FT /evidence="ECO:0000255"
FT REPEAT 201..227
FT /note="HEAT-like PBS-type 3"
FT /evidence="ECO:0000255"
FT REPEAT 234..260
FT /note="HEAT-like PBS-type 4"
FT /evidence="ECO:0000255"
FT REPEAT 267..293
FT /note="HEAT-like PBS-type 5"
FT /evidence="ECO:0000255"
FT REGION 169..179
FT /note="Required for enzyme activity"
FT /evidence="ECO:0000269|PubMed:22438895"
FT BINDING 64
FT /ligand="Fe cation"
FT /ligand_id="ChEBI:CHEBI:24875"
FT /ligand_label="1"
FT /evidence="ECO:0000250|UniProtKB:Q9BU89, ECO:0000255|HAMAP-
FT Rule:MF_03101"
FT BINDING 97
FT /ligand="Fe cation"
FT /ligand_id="ChEBI:CHEBI:24875"
FT /ligand_label="2"
FT /evidence="ECO:0000250|UniProtKB:Q9BU89, ECO:0000255|HAMAP-
FT Rule:MF_03101"
FT BINDING 98
FT /ligand="Fe cation"
FT /ligand_id="ChEBI:CHEBI:24875"
FT /ligand_label="2"
FT /evidence="ECO:0000250|UniProtKB:Q9BU89, ECO:0000255|HAMAP-
FT Rule:MF_03101"
FT BINDING 236
FT /ligand="Fe cation"
FT /ligand_id="ChEBI:CHEBI:24875"
FT /ligand_label="2"
FT /evidence="ECO:0000250|UniProtKB:Q9BU89, ECO:0000255|HAMAP-
FT Rule:MF_03101"
FT BINDING 269
FT /ligand="Fe cation"
FT /ligand_id="ChEBI:CHEBI:24875"
FT /ligand_label="1"
FT /evidence="ECO:0000250|UniProtKB:Q9BU89, ECO:0000255|HAMAP-
FT Rule:MF_03101"
FT BINDING 270
FT /ligand="Fe cation"
FT /ligand_id="ChEBI:CHEBI:24875"
FT /ligand_label="1"
FT /evidence="ECO:0000250|UniProtKB:Q9BU89, ECO:0000255|HAMAP-
FT Rule:MF_03101"
SQ SEQUENCE 326 AA; 35753 MW; D42F898C9B896A3F CRC64;
MSALNSRTVE EVRKDYAKLL DPQEPLDSRM RELYRLKEDC LKTAAGVTVI LETIDTTDSV
LLQHELAYNA GQSGREEAVP ELERILRTTS YDVVTRHEAA EALGAIGSPL ALQVLEAHSD
PTTEPEAPIR ETCELALARI AMKETKGDAA VAPPSGCEFV SVDPSPAFSA LYSSTDEPVP
HTVEELEAVL LDTSGRTRLF RRYMAMFTLR NLATEAAVAA LCRGLREDNV SALFRHEVAF
VLGQLERPSS QPALIAALKD EEEAPMVRHE AAEALGAIAD PATLPVLESY ATHHEPIVRD
SCVVALEMHK YWANFNGLAH QQQQEA
