DDAH_PSEAE
ID DDAH_PSEAE Reviewed; 254 AA.
AC Q9I4E3;
DT 05-OCT-2010, integrated into UniProtKB/Swiss-Prot.
DT 01-MAR-2001, sequence version 1.
DT 03-AUG-2022, entry version 108.
DE RecName: Full=N(G),N(G)-dimethylarginine dimethylaminohydrolase {ECO:0000305};
DE Short=DDAH {ECO:0000303|PubMed:10510241};
DE Short=Dimethylarginine dimethylaminohydrolase {ECO:0000303|PubMed:10510241};
DE EC=3.5.3.18 {ECO:0000269|PubMed:10510241, ECO:0000269|PubMed:11473257, ECO:0000269|PubMed:16634643};
DE AltName: Full=Dimethylargininase {ECO:0000303|PubMed:16634643};
GN OrderedLocusNames=PA1195;
OS Pseudomonas aeruginosa (strain ATCC 15692 / DSM 22644 / CIP 104116 / JCM
OS 14847 / LMG 12228 / 1C / PRS 101 / PAO1).
OC Bacteria; Proteobacteria; Gammaproteobacteria; Pseudomonadales;
OC Pseudomonadaceae; Pseudomonas.
OX NCBI_TaxID=208964;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=ATCC 15692 / DSM 22644 / CIP 104116 / JCM 14847 / LMG 12228 / 1C /
RC PRS 101 / PAO1;
RX PubMed=10984043; DOI=10.1038/35023079;
RA Stover C.K., Pham X.-Q.T., Erwin A.L., Mizoguchi S.D., Warrener P.,
RA Hickey M.J., Brinkman F.S.L., Hufnagle W.O., Kowalik D.J., Lagrou M.,
RA Garber R.L., Goltry L., Tolentino E., Westbrock-Wadman S., Yuan Y.,
RA Brody L.L., Coulter S.N., Folger K.R., Kas A., Larbig K., Lim R.M.,
RA Smith K.A., Spencer D.H., Wong G.K.-S., Wu Z., Paulsen I.T., Reizer J.,
RA Saier M.H. Jr., Hancock R.E.W., Lory S., Olson M.V.;
RT "Complete genome sequence of Pseudomonas aeruginosa PAO1, an opportunistic
RT pathogen.";
RL Nature 406:959-964(2000).
RN [2]
RP FUNCTION, AND CATALYTIC ACTIVITY.
RX PubMed=10510241; DOI=10.1046/j.1365-2958.1999.01580.x;
RA Santa Maria J., Vallance P., Charles I.G., Leiper J.M.;
RT "Identification of microbial dimethylarginine dimethylaminohydrolase
RT enzymes.";
RL Mol. Microbiol. 33:1278-1279(1999).
RN [3]
RP FUNCTION, CATALYTIC ACTIVITY, ACTIVITY REGULATION, ZINC BINDING SITES,
RP ACTIVE SITE, IDENTIFICATION BY MASS SPECTROMETRY, BIOPHYSICOCHEMICAL
RP PROPERTIES, AND MUTAGENESIS OF HIS-162 AND CYS-249.
RX PubMed=16634643; DOI=10.1021/bi052595m;
RA Stone E.M., Costello A.L., Tierney D.L., Fast W.;
RT "Substrate-assisted cysteine deprotonation in the mechanism of
RT dimethylargininase (DDAH) from Pseudomonas aeruginosa.";
RL Biochemistry 45:5618-5630(2006).
RN [4] {ECO:0007744|PDB:1H70}
RP X-RAY CRYSTALLOGRAPHY (1.8 ANGSTROMS) OF MUTANT SER-249 IN COMPLEX WITH
RP CITRULLINE, CATALYTIC ACTIVITY, ACTIVE SITE, SUBUNIT, AND MUTAGENESIS OF
RP GLU-114; HIS-162 AND CYS-249.
RX PubMed=11473257; DOI=10.1038/90387;
RA Murray-Rust J., Leiper J., McAlister M., Phelan J., Tilley S.,
RA Santa Maria J., Vallance P., McDonald N.;
RT "Structural insights into the hydrolysis of cellular nitric oxide synthase
RT inhibitors by dimethylarginine dimethylaminohydrolase.";
RL Nat. Struct. Biol. 8:679-683(2001).
RN [5] {ECO:0007744|PDB:3BPB}
RP X-RAY CRYSTALLOGRAPHY (2.81 ANGSTROMS) OF MUTANT GLY-162 IN COMPLEX WITH
RP S-METHYL-L-THIOCITRULLIN, ACTIVE SITE, AND SUBUNIT.
RX PubMed=18482699; DOI=10.1016/j.chembiol.2008.03.012;
RA Linsky T.W., Monzingo A.F., Stone E.M., Robertus J.D., Fast W.;
RT "Promiscuous partitioning of a covalent intermediate common in the pentein
RT superfamily.";
RL Chem. Biol. 15:467-475(2008).
CC -!- FUNCTION: Hydrolyzes N(G),N(G)-dimethyl-L-arginine (ADMA) and N(G)-
CC monomethyl-L-arginine (MMA). {ECO:0000269|PubMed:10510241,
CC ECO:0000269|PubMed:16634643}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=H2O + N(omega),N(omega)-dimethyl-L-arginine = dimethylamine +
CC L-citrulline; Xref=Rhea:RHEA:17305, ChEBI:CHEBI:15377,
CC ChEBI:CHEBI:57743, ChEBI:CHEBI:58040, ChEBI:CHEBI:58326; EC=3.5.3.18;
CC Evidence={ECO:0000269|PubMed:10510241, ECO:0000269|PubMed:11473257,
CC ECO:0000269|PubMed:16634643};
CC -!- ACTIVITY REGULATION: Inhibited by zinc ions. Competitively inhibited by
CC lysine. {ECO:0000269|PubMed:16634643}.
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=44 uM for N-methyl-L-arginine {ECO:0000269|PubMed:16634643};
CC KM=39 uM for N,N-dimethyl-L-arginine {ECO:0000269|PubMed:16634643};
CC KM=26 uM for S-methyl-L-thiocitrulline {ECO:0000269|PubMed:16634643};
CC pH dependence:
CC Optimum pH is 7-8.5. {ECO:0000269|PubMed:16634643};
CC -!- SUBUNIT: Homodimer. {ECO:0000269|PubMed:11473257,
CC ECO:0000269|PubMed:18482699}.
CC -!- SIMILARITY: Belongs to the DDAH family. {ECO:0000305}.
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DR EMBL; AE004091; AAG04584.1; -; Genomic_DNA.
DR PIR; F83497; F83497.
DR RefSeq; NP_249886.1; NC_002516.2.
DR RefSeq; WP_003086612.1; NZ_QZGE01000006.1.
DR PDB; 1H70; X-ray; 1.80 A; A=1-254.
DR PDB; 3BPB; X-ray; 2.81 A; A/B=1-254.
DR PDB; 3RHY; X-ray; 2.18 A; A/B=1-254.
DR PDBsum; 1H70; -.
DR PDBsum; 3BPB; -.
DR PDBsum; 3RHY; -.
DR AlphaFoldDB; Q9I4E3; -.
DR BMRB; Q9I4E3; -.
DR SMR; Q9I4E3; -.
DR STRING; 287.DR97_739; -.
DR PaxDb; Q9I4E3; -.
DR PRIDE; Q9I4E3; -.
DR EnsemblBacteria; AAG04584; AAG04584; PA1195.
DR GeneID; 883112; -.
DR KEGG; pae:PA1195; -.
DR PATRIC; fig|208964.12.peg.1241; -.
DR PseudoCAP; PA1195; -.
DR HOGENOM; CLU_067923_1_0_6; -.
DR InParanoid; Q9I4E3; -.
DR OMA; HRYTHAI; -.
DR PhylomeDB; Q9I4E3; -.
DR BioCyc; PAER208964:G1FZ6-1220-MON; -.
DR BRENDA; 3.5.3.18; 5087.
DR EvolutionaryTrace; Q9I4E3; -.
DR Proteomes; UP000002438; Chromosome.
DR GO; GO:0016597; F:amino acid binding; IBA:GO_Central.
DR GO; GO:0016403; F:dimethylargininase activity; IBA:GO_Central.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0006525; P:arginine metabolic process; IBA:GO_Central.
DR GO; GO:0000052; P:citrulline metabolic process; IBA:GO_Central.
DR GO; GO:0045429; P:positive regulation of nitric oxide biosynthetic process; IBA:GO_Central.
DR InterPro; IPR033199; DDAH.
DR PANTHER; PTHR12737; PTHR12737; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Hydrolase; Metal-binding; Reference proteome; Zinc.
FT CHAIN 1..254
FT /note="N(G),N(G)-dimethylarginine dimethylaminohydrolase"
FT /id="PRO_0000398677"
FT ACT_SITE 162
FT /note="Proton donor"
FT /evidence="ECO:0000305|PubMed:11473257,
FT ECO:0000305|PubMed:16634643, ECO:0000305|PubMed:18482699"
FT ACT_SITE 249
FT /note="Nucleophile"
FT /evidence="ECO:0000305|PubMed:11473257,
FT ECO:0000305|PubMed:16634643, ECO:0000305|PubMed:18482699"
FT BINDING 18
FT /ligand="substrate"
FT /evidence="ECO:0000305|PubMed:11473257"
FT BINDING 60
FT /ligand="substrate"
FT /evidence="ECO:0000305|PubMed:11473257"
FT BINDING 65..66
FT /ligand="substrate"
FT /evidence="ECO:0000305|PubMed:11473257"
FT BINDING 85
FT /ligand="substrate"
FT /evidence="ECO:0000305|PubMed:11473257"
FT BINDING 132
FT /ligand="substrate"
FT /evidence="ECO:0000305|PubMed:11473257"
FT BINDING 162
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000305|PubMed:16634643"
FT BINDING 243
FT /ligand="substrate"
FT /evidence="ECO:0000305|PubMed:11473257"
FT BINDING 249
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000305|PubMed:16634643"
FT MUTAGEN 114
FT /note="E->Q: Abolishes enzyme activity."
FT /evidence="ECO:0000269|PubMed:11473257"
FT MUTAGEN 162
FT /note="H->G,F: Abolishes enzyme activity."
FT /evidence="ECO:0000269|PubMed:11473257,
FT ECO:0000269|PubMed:16634643"
FT MUTAGEN 249
FT /note="C->S: Abolishes enzyme activity."
FT /evidence="ECO:0000269|PubMed:11473257,
FT ECO:0000269|PubMed:16634643"
FT STRAND 4..8
FT /evidence="ECO:0007829|PDB:1H70"
FT HELIX 12..16
FT /evidence="ECO:0007829|PDB:1H70"
FT STRAND 21..23
FT /evidence="ECO:0007829|PDB:3BPB"
FT HELIX 28..42
FT /evidence="ECO:0007829|PDB:1H70"
FT TURN 43..46
FT /evidence="ECO:0007829|PDB:3BPB"
FT STRAND 48..52
FT /evidence="ECO:0007829|PDB:1H70"
FT TURN 59..62
FT /evidence="ECO:0007829|PDB:1H70"
FT TURN 64..67
FT /evidence="ECO:0007829|PDB:1H70"
FT STRAND 68..70
FT /evidence="ECO:0007829|PDB:1H70"
FT STRAND 75..77
FT /evidence="ECO:0007829|PDB:1H70"
FT HELIX 83..87
FT /evidence="ECO:0007829|PDB:1H70"
FT HELIX 88..99
FT /evidence="ECO:0007829|PDB:1H70"
FT STRAND 104..106
FT /evidence="ECO:0007829|PDB:1H70"
FT HELIX 115..117
FT /evidence="ECO:0007829|PDB:1H70"
FT STRAND 118..121
FT /evidence="ECO:0007829|PDB:1H70"
FT STRAND 124..129
FT /evidence="ECO:0007829|PDB:1H70"
FT STRAND 131..133
FT /evidence="ECO:0007829|PDB:1H70"
FT HELIX 135..147
FT /evidence="ECO:0007829|PDB:1H70"
FT STRAND 151..156
FT /evidence="ECO:0007829|PDB:1H70"
FT STRAND 158..162
FT /evidence="ECO:0007829|PDB:1H70"
FT HELIX 163..165
FT /evidence="ECO:0007829|PDB:1H70"
FT STRAND 166..169
FT /evidence="ECO:0007829|PDB:1H70"
FT STRAND 174..177
FT /evidence="ECO:0007829|PDB:1H70"
FT HELIX 179..181
FT /evidence="ECO:0007829|PDB:1H70"
FT HELIX 185..187
FT /evidence="ECO:0007829|PDB:1H70"
FT STRAND 190..194
FT /evidence="ECO:0007829|PDB:1H70"
FT HELIX 197..203
FT /evidence="ECO:0007829|PDB:1H70"
FT STRAND 206..208
FT /evidence="ECO:0007829|PDB:1H70"
FT STRAND 211..217
FT /evidence="ECO:0007829|PDB:1H70"
FT HELIX 219..226
FT /evidence="ECO:0007829|PDB:1H70"
FT TURN 227..229
FT /evidence="ECO:0007829|PDB:1H70"
FT STRAND 231..235
FT /evidence="ECO:0007829|PDB:1H70"
FT HELIX 238..241
FT /evidence="ECO:0007829|PDB:1H70"
FT TURN 242..244
FT /evidence="ECO:0007829|PDB:1H70"
FT TURN 247..250
FT /evidence="ECO:0007829|PDB:1H70"
FT STRAND 252..254
FT /evidence="ECO:0007829|PDB:1H70"
SQ SEQUENCE 254 AA; 28470 MW; 28E9FC2F61E3EBE2 CRC64;
MFKHIIARTP ARSLVDGLTS SHLGKPDYAK ALEQHNAYIR ALQTCDVDIT LLPPDERFPD
SVFVEDPVLC TSRCAIITRP GAESRRGETE IIEETVQRFY PGKVERIEAP GTVEAGDIMM
VGDHFYIGES ARTNAEGARQ MIAILEKHGL SGSVVRLEKV LHLKTGLAYL EHNNLLAAGE
FVSKPEFQDF NIIEIPEEES YAANCIWVNE RVIMPAGYPR TREKIARLGY RVIEVDTSEY
RKIDGGVSCM SLRF
