DPH2_PYRHO
ID DPH2_PYRHO Reviewed; 342 AA.
AC O58832;
DT 03-MAY-2011, integrated into UniProtKB/Swiss-Prot.
DT 01-AUG-1998, sequence version 1.
DT 03-AUG-2022, entry version 113.
DE RecName: Full=2-(3-amino-3-carboxypropyl)histidine synthase;
DE EC=2.5.1.108 {ECO:0000269|PubMed:20559380};
DE AltName: Full=Diphthamide biosynthesis protein Dph2;
DE AltName: Full=S-adenosyl-L-methionine:L-histidine 3-amino-3-carboxypropyltransferase;
GN Name=dph2; OrderedLocusNames=PH1105;
OS Pyrococcus horikoshii (strain ATCC 700860 / DSM 12428 / JCM 9974 / NBRC
OS 100139 / OT-3).
OC Archaea; Euryarchaeota; Thermococci; Thermococcales; Thermococcaceae;
OC Pyrococcus.
OX NCBI_TaxID=70601;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=ATCC 700860 / DSM 12428 / JCM 9974 / NBRC 100139 / OT-3;
RX PubMed=9679194; DOI=10.1093/dnares/5.2.55;
RA Kawarabayasi Y., Sawada M., Horikawa H., Haikawa Y., Hino Y., Yamamoto S.,
RA Sekine M., Baba S., Kosugi H., Hosoyama A., Nagai Y., Sakai M., Ogura K.,
RA Otsuka R., Nakazawa H., Takamiya M., Ohfuku Y., Funahashi T., Tanaka T.,
RA Kudoh Y., Yamazaki J., Kushida N., Oguchi A., Aoki K., Yoshizawa T.,
RA Nakamura Y., Robb F.T., Horikoshi K., Masuchi Y., Shizuya H., Kikuchi H.;
RT "Complete sequence and gene organization of the genome of a hyper-
RT thermophilic archaebacterium, Pyrococcus horikoshii OT3.";
RL DNA Res. 5:55-76(1998).
RN [2]
RP REACTION MECHANISM, AND MUTAGENESIS OF CYS-59; CYS-163 AND CYS-287.
RX PubMed=20931132; DOI=10.1039/c0mb00076k;
RA Zhu X., Dzikovski B., Su X., Torelli A.T., Zhang Y., Ealick S.E.,
RA Freed J.H., Lin H.;
RT "Mechanistic understanding of Pyrococcus horikoshii Dph2, a [4Fe-4S] enzyme
RT required for diphthamide biosynthesis.";
RL Mol. Biosyst. 7:74-81(2011).
RN [3]
RP X-RAY CRYSTALLOGRAPHY (2.10 ANGSTROMS) OF NATIVE PROTEIN AND IN COMPLEX
RP WITH IRON-SULFUR (4FE-4S) CLUSTER, FUNCTION, CATALYTIC ACTIVITY, COFACTOR,
RP SUBUNIT, PATHWAY, AND REACTION MECHANISM.
RX PubMed=20559380; DOI=10.1038/nature09138;
RA Zhang Y., Zhu X., Torelli A.T., Lee M., Dzikovski B., Koralewski R.M.,
RA Wang E., Freed J., Krebs C., Ealick S.E., Lin H.;
RT "Diphthamide biosynthesis requires an organic radical generated by an iron-
RT sulphur enzyme.";
RL Nature 465:891-896(2010).
CC -!- FUNCTION: Catalyzes the first step of diphthamide biosynthesis, i.e.
CC the transfer of the 3-amino-3-carboxypropyl group from S-adenosyl-L-
CC methionine (SAM) to the C2 position of the imidazole ring of the target
CC histidine residue in translation elongation factor 2 (EF-2).
CC {ECO:0000269|PubMed:20559380}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=L-histidyl-[translation elongation factor 2] + S-adenosyl-L-
CC methionine = 2-[(3S)-amino-3-carboxypropyl]-L-histidyl-[translation
CC elongation factor 2] + H(+) + S-methyl-5'-thioadenosine;
CC Xref=Rhea:RHEA:36783, Rhea:RHEA-COMP:9748, Rhea:RHEA-COMP:9749,
CC ChEBI:CHEBI:15378, ChEBI:CHEBI:17509, ChEBI:CHEBI:29979,
CC ChEBI:CHEBI:59789, ChEBI:CHEBI:73995; EC=2.5.1.108;
CC Evidence={ECO:0000269|PubMed:20559380};
CC -!- COFACTOR:
CC Name=[4Fe-4S] cluster; Xref=ChEBI:CHEBI:49883;
CC Evidence={ECO:0000269|PubMed:20559380};
CC Note=Binds 1 [4Fe-4S] cluster per subunit. The cluster is coordinated
CC with 3 cysteines and an exchangeable S-adenosyl-L-methionine.
CC {ECO:0000269|PubMed:20559380};
CC -!- PATHWAY: Protein modification; peptidyl-diphthamide biosynthesis.
CC {ECO:0000269|PubMed:20559380}.
CC -!- SUBUNIT: Homodimer. {ECO:0000269|PubMed:20559380}.
CC -!- MISCELLANEOUS: Unlike the enzymes in the radical SAM superfamily, Dph2
CC does not form the canonical 5'-deoxyadenosyl radical. Instead, it
CC breaks the C(gamma)-S bond of SAM and generates a 3-amino-3-
CC carboxypropyl radical intermediate. Thus, the P.horikoshii Dph2
CC represents a previously unknown, SAM-dependent, [4Fe-4S]-containing
CC enzyme that catalyzes unprecedented chemistry. Moreover, the chemistry
CC requires only one [4Fe-4S] cluster to be present in the Dph2 dimer,
CC although each monomer can bind a [4Fe-4S] cluster.
CC {ECO:0000303|PubMed:20931132}.
CC -!- MISCELLANEOUS: In contrast to eukaryotes that require four gene
CC products (DPH1, DPH2, DPH3 and DPH4) to catalyze the first step of
CC diphthamide biosynthesis, no other protein than Dph2 is required in
CC P.horikoshii.
CC -!- SIMILARITY: Belongs to the DPH1/DPH2 family. {ECO:0000305}.
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DR EMBL; BA000001; BAA30204.1; -; Genomic_DNA.
DR PIR; B71051; B71051.
DR RefSeq; WP_010885188.1; NC_000961.1.
DR PDB; 3LZC; X-ray; 2.26 A; A/B=1-342.
DR PDB; 3LZD; X-ray; 2.10 A; A/B=1-342.
DR PDB; 6BXK; X-ray; 2.35 A; A/B=1-342.
DR PDB; 6BXL; X-ray; 2.30 A; A/B=1-342.
DR PDBsum; 3LZC; -.
DR PDBsum; 3LZD; -.
DR PDBsum; 6BXK; -.
DR PDBsum; 6BXL; -.
DR AlphaFoldDB; O58832; -.
DR SMR; O58832; -.
DR STRING; 70601.3257521; -.
DR EnsemblBacteria; BAA30204; BAA30204; BAA30204.
DR GeneID; 1443423; -.
DR KEGG; pho:PH1105; -.
DR eggNOG; arCOG04112; Archaea.
DR OMA; PGQVLGC; -.
DR OrthoDB; 87520at2157; -.
DR BioCyc; MetaCyc:MON-18826; -.
DR BRENDA; 2.5.1.108; 5244.
DR UniPathway; UPA00559; -.
DR EvolutionaryTrace; O58832; -.
DR Proteomes; UP000000752; Chromosome.
DR GO; GO:0090560; F:2-(3-amino-3-carboxypropyl)histidine synthase activity; IEA:UniProtKB-EC.
DR GO; GO:0051539; F:4 iron, 4 sulfur cluster binding; IDA:UniProtKB.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0016765; F:transferase activity, transferring alkyl or aryl (other than methyl) groups; IDA:UniProtKB.
DR GO; GO:0017183; P:peptidyl-diphthamide biosynthetic process from peptidyl-histidine; IDA:UniProtKB.
DR GO; GO:0050843; P:S-adenosylmethionine catabolic process; IDA:UniProtKB.
DR Gene3D; 3.40.50.11840; -; 1.
DR Gene3D; 3.40.50.11850; -; 1.
DR Gene3D; 3.40.50.11860; -; 1.
DR InterPro; IPR016435; DPH1/DPH2.
DR InterPro; IPR042263; DPH1/DPH2_1.
DR InterPro; IPR042264; DPH1/DPH2_2.
DR InterPro; IPR042265; DPH1/DPH2_3.
DR InterPro; IPR035435; DPH1/DPH2_euk_archaea.
DR InterPro; IPR022428; Dph2_arc.
DR PANTHER; PTHR10762; PTHR10762; 1.
DR Pfam; PF01866; Diphthamide_syn; 1.
DR PIRSF; PIRSF004967; DPH1; 1.
DR SFLD; SFLDS00032; Radical_SAM_3-amino-3-carboxyp; 1.
DR TIGRFAMs; TIGR03682; arCOG04112; 1.
DR TIGRFAMs; TIGR00322; diphth2_R; 1.
PE 1: Evidence at protein level;
KW 3D-structure; 4Fe-4S; Iron; Iron-sulfur; Metal-binding;
KW S-adenosyl-L-methionine; Transferase.
FT CHAIN 1..342
FT /note="2-(3-amino-3-carboxypropyl)histidine synthase"
FT /id="PRO_0000407844"
FT BINDING 59
FT /ligand="[4Fe-4S] cluster"
FT /ligand_id="ChEBI:CHEBI:49883"
FT BINDING 163
FT /ligand="[4Fe-4S] cluster"
FT /ligand_id="ChEBI:CHEBI:49883"
FT BINDING 287
FT /ligand="[4Fe-4S] cluster"
FT /ligand_id="ChEBI:CHEBI:49883"
FT MUTAGEN 59
FT /note="C->A: Still able to bind a 4Fe-4S cluster. Less
FT active than wild-type. Not able to bind a 4Fe-4S cluster
FT and loss of catalytic activity; when associated with Ala-
FT 287."
FT /evidence="ECO:0000269|PubMed:20931132"
FT MUTAGEN 163
FT /note="C->A: Still able to bind a 4Fe-4S cluster. Less
FT active than wild-type."
FT /evidence="ECO:0000269|PubMed:20931132"
FT MUTAGEN 287
FT /note="C->A: Still able to bind a 4Fe-4S cluster. Less
FT active than wild-type. Not able to bind a 4Fe-4S cluster
FT and loss of catalytic activity; when associated with Ala-
FT 59."
FT /evidence="ECO:0000269|PubMed:20931132"
FT HELIX 7..16
FT /evidence="ECO:0007829|PDB:3LZD"
FT STRAND 21..25
FT /evidence="ECO:0007829|PDB:3LZD"
FT HELIX 28..30
FT /evidence="ECO:0007829|PDB:3LZD"
FT HELIX 31..42
FT /evidence="ECO:0007829|PDB:3LZD"
FT TURN 43..45
FT /evidence="ECO:0007829|PDB:3LZD"
FT STRAND 47..51
FT /evidence="ECO:0007829|PDB:3LZD"
FT HELIX 63..68
FT /evidence="ECO:0007829|PDB:3LZD"
FT STRAND 72..78
FT /evidence="ECO:0007829|PDB:3LZD"
FT STRAND 90..94
FT /evidence="ECO:0007829|PDB:3LZD"
FT HELIX 102..107
FT /evidence="ECO:0007829|PDB:3LZD"
FT HELIX 109..113
FT /evidence="ECO:0007829|PDB:3LZD"
FT STRAND 117..123
FT /evidence="ECO:0007829|PDB:3LZD"
FT HELIX 125..130
FT /evidence="ECO:0007829|PDB:3LZD"
FT HELIX 131..140
FT /evidence="ECO:0007829|PDB:3LZD"
FT STRAND 144..146
FT /evidence="ECO:0007829|PDB:3LZD"
FT HELIX 166..168
FT /evidence="ECO:0007829|PDB:3LZD"
FT STRAND 173..182
FT /evidence="ECO:0007829|PDB:3LZD"
FT HELIX 183..192
FT /evidence="ECO:0007829|PDB:3LZD"
FT STRAND 194..199
FT /evidence="ECO:0007829|PDB:3LZD"
FT TURN 201..203
FT /evidence="ECO:0007829|PDB:3LZD"
FT STRAND 206..208
FT /evidence="ECO:0007829|PDB:3LZD"
FT HELIX 212..225
FT /evidence="ECO:0007829|PDB:3LZD"
FT STRAND 230..236
FT /evidence="ECO:0007829|PDB:3LZD"
FT TURN 239..241
FT /evidence="ECO:0007829|PDB:3LZD"
FT HELIX 244..256
FT /evidence="ECO:0007829|PDB:3LZD"
FT STRAND 260..268
FT /evidence="ECO:0007829|PDB:3LZD"
FT HELIX 271..274
FT /evidence="ECO:0007829|PDB:3LZD"
FT STRAND 280..284
FT /evidence="ECO:0007829|PDB:3LZD"
FT HELIX 289..292
FT /evidence="ECO:0007829|PDB:3LZD"
FT HELIX 305..311
FT /evidence="ECO:0007829|PDB:3LZD"
FT STRAND 337..339
FT /evidence="ECO:0007829|PDB:3LZD"
SQ SEQUENCE 342 AA; 38464 MW; 5DDE0E90B88EE553 CRC64;
MLHEIPKSEI LKELKRIGAK RVLIQSPEGL RREAEELAGF LEENNIEVFL HGEINYGACD
PADREAKLVG CDALIHLGHS YMKLPLEVPT IFVPAFARVS VVEALKENIG EIKKLGRKII
VTTTAQHIHQ LKEAKEFLES EGFEVSIGRG DSRISWPGQV LGCNYSVAKV RGEGILFIGS
GIFHPLGLAV ATRKKVLAID PYTKAFSWID PERFIRKRWA QIAKAMDAKK FGVIVSIKKG
QLRLAEAKRI VKLLKKHGRE ARLIVMNDVN YHKLEGFPFE AYVVVACPRV PLDDYGAWRK
PVLTPKEVEI LLGLREEYEF DEILGGPRES DEPFGISIHS TR
