DHYS_LEIDO
ID DHYS_LEIDO Reviewed; 601 AA.
AC B5APK2;
DT 31-OCT-2012, integrated into UniProtKB/Swiss-Prot.
DT 23-SEP-2008, sequence version 1.
DT 03-AUG-2022, entry version 42.
DE RecName: Full=Deoxyhypusine synthase {ECO:0000250|UniProtKB:P49366, ECO:0000312|EMBL:ACF75531.1};
DE Short=DHS {ECO:0000250|UniProtKB:P49366};
DE EC=2.5.1.46 {ECO:0000250|UniProtKB:P49366};
DE AltName: Full=Deoxyhypusine synthase from chromosome 34 {ECO:0000303|PubMed:19880510};
DE Short=DHS34 {ECO:0000303|PubMed:19880510};
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:ACF75531.1}
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], CATALYTIC ACTIVITY, ACTIVITY REGULATION,
RP BIOPHYSICOCHEMICAL PROPERTIES, HOMODIMERIZATION, AND 3D-STRUCTURE MODELING.
RX PubMed=19880510; DOI=10.1074/jbc.m109.048850;
RA Chawla B., Jhingran A., Singh S., Tyagi N., Park M.H., Srinivasan N.,
RA Roberts S.C., Madhubala R.;
RT "Identification and characterization of a novel deoxyhypusine synthase in
RT Leishmania donovani.";
RL J. Biol. Chem. 285:453-463(2010).
CC -!- FUNCTION: Catalyzes the NAD-dependent oxidative cleavage of spermidine
CC and the subsequent transfer of the butylamine moiety of spermidine to
CC the epsilon-amino group of a specific lysine residue of the eIF-5A
CC precursor protein to form the intermediate deoxyhypusine residue.
CC {ECO:0000250|UniProtKB:P49366}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=[eIF5A protein]-L-lysine + spermidine = [eIF5A protein]-
CC deoxyhypusine + propane-1,3-diamine; Xref=Rhea:RHEA:33299, Rhea:RHEA-
CC COMP:10143, Rhea:RHEA-COMP:10144, ChEBI:CHEBI:29969,
CC ChEBI:CHEBI:57484, ChEBI:CHEBI:57834, ChEBI:CHEBI:82657; EC=2.5.1.46;
CC Evidence={ECO:0000250|UniProtKB:P49366, ECO:0000269|PubMed:19880510};
CC -!- COFACTOR:
CC Name=NAD(+); Xref=ChEBI:CHEBI:57540;
CC Evidence={ECO:0000250|UniProtKB:P49366};
CC -!- ACTIVITY REGULATION: N1-guanyl-1,7-diaminoheptane has a small
CC inhibitory effect on activity. {ECO:0000269|PubMed:19880510}.
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=1.77 uM for eIF5A {ECO:0000269|PubMed:19880510};
CC KM=23.2 uM for spermidine {ECO:0000269|PubMed:19880510};
CC Vmax=569 pmol/h/mg enzyme for the forward reaction
CC {ECO:0000269|PubMed:19880510};
CC -!- PATHWAY: Protein modification; eIF5A hypusination. {ECO:0000305}.
CC -!- SUBUNIT: Homodimer. {ECO:0000269|PubMed:19880510}.
CC -!- SIMILARITY: Belongs to the deoxyhypusine synthase family.
CC {ECO:0000255}.
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DR EMBL; EU864544; ACF75531.1; -; Genomic_DNA.
DR AlphaFoldDB; B5APK2; -.
DR SMR; B5APK2; -.
DR VEuPathDB; TriTrypDB:LdBPK_340350.1; -.
DR VEuPathDB; TriTrypDB:LdCL_340008600; -.
DR VEuPathDB; TriTrypDB:LDHU3_34.0520; -.
DR BRENDA; 2.5.1.46; 2947.
DR SABIO-RK; B5APK2; -.
DR UniPathway; UPA00354; -.
DR GO; GO:0034038; F:deoxyhypusine synthase activity; IEA:UniProtKB-EC.
DR GO; GO:0042803; F:protein homodimerization activity; 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; 3.40.910.10; -; 2.
DR InterPro; IPR002773; Deoxyhypusine_synthase.
DR InterPro; IPR036982; Deoxyhypusine_synthase_sf.
DR InterPro; IPR029035; DHS-like_NAD/FAD-binding_dom.
DR PANTHER; PTHR11703; PTHR11703; 1.
DR Pfam; PF01916; DS; 2.
DR SUPFAM; SSF52467; SSF52467; 1.
PE 1: Evidence at protein level;
KW Hypusine biosynthesis; NAD; Transferase.
FT CHAIN 1..601
FT /note="Deoxyhypusine synthase"
FT /id="PRO_0000419760"
FT REGION 210..242
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 411..451
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 568..601
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 210..224
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 570..585
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT ACT_SITE 535
FT /note="Nucleophile"
FT /evidence="ECO:0000250|UniProtKB:P49366"
FT BINDING 109..113
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /evidence="ECO:0000250|UniProtKB:P49366"
FT BINDING 184..186
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /evidence="ECO:0000250|UniProtKB:P49366"
FT BINDING 189..190
FT /ligand="spermidine"
FT /ligand_id="ChEBI:CHEBI:57834"
FT /evidence="ECO:0000250|UniProtKB:P49366"
FT BINDING 398
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /evidence="ECO:0000250|UniProtKB:P49366"
FT BINDING 489
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /evidence="ECO:0000250|UniProtKB:P49366"
FT BINDING 494
FT /ligand="spermidine"
FT /ligand_id="ChEBI:CHEBI:57834"
FT /evidence="ECO:0000250|UniProtKB:P49366"
FT BINDING 514..515
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /evidence="ECO:0000250|UniProtKB:P49366"
FT BINDING 520..522
FT /ligand="spermidine"
FT /ligand_id="ChEBI:CHEBI:57834"
FT /evidence="ECO:0000250|UniProtKB:P49366"
FT BINDING 529..535
FT /ligand="spermidine"
FT /ligand_id="ChEBI:CHEBI:57834"
FT /evidence="ECO:0000250|UniProtKB:P49366"
FT BINDING 548..549
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /evidence="ECO:0000250|UniProtKB:P49366"
SQ SEQUENCE 601 AA; 64440 MW; A2E853EA8367C831 CRC64;
MANIAESAVL VSSASSAQAV AKLTQVRGPT SGFDKAQHII GSYSTMGFQA TNYGLARSIA
QRMIRKQPPS KVYQIKDGKY VLVPPDVGED GKTLQQEHVY PNLFMGVTAN LMGTGCREAV
RFLVQEGVVH RSLEASAPAS ADGTDDQLMF ARLKREYVET YGGPPHPDEE IPRAHSFLCA
IVVSGGGVEH DLRRACTAYT LHHYASEAQG HVSSTVSSEA TAPPKGLQQR AEKPLGTRAA
AGTAKPARFG NVEYPRQGST GSELFDCLMR TFVQRLCARQ ARLRAAAMAK PIPDKYDDVC
SWSVTPSEVW ALCGLWLVDM LAEALGAVRS CTSRLTSGSA VGTAESVTAN GKGPEADRDA
HIATSASYRA EALARARTTV VYWAALQQVS LFSPSFVDGD ITSYLLPTPA PAARPAHRKG
GPVADENAGN SKELKRSRKA SSSSSTSATA VKVKPPVVER LQVDLVRDVY SINKLAMLSK
KTGMLICGGG VVKHHVCNAN LMRNGADFTI ILSNGQEFDG SDAGAKPEEA LSWGKVRMEG
AFVKVYGEVS TYLPLLLAEV FVPAVRQRRA TDDAQPRRKR SSRGARPPQD VSGHSHLCRG
E
