P4H_RHILO
ID P4H_RHILO Reviewed; 280 AA.
AC Q989T9;
DT 20-APR-2010, integrated into UniProtKB/Swiss-Prot.
DT 01-OCT-2001, sequence version 1.
DT 03-AUG-2022, entry version 100.
DE RecName: Full=L-proline cis-4-hydroxylase;
DE Short=P4H;
DE EC=1.14.11.56 {ECO:0000269|PubMed:19133227};
GN OrderedLocusNames=mlr6283;
OS Mesorhizobium japonicum (strain LMG 29417 / CECT 9101 / MAFF 303099)
OS (Mesorhizobium loti (strain MAFF 303099)).
OC Bacteria; Proteobacteria; Alphaproteobacteria; Hyphomicrobiales;
OC Phyllobacteriaceae; Mesorhizobium.
OX NCBI_TaxID=266835;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=LMG 29417 / CECT 9101 / MAFF 303099;
RX PubMed=11214968; DOI=10.1093/dnares/7.6.331;
RA Kaneko T., Nakamura Y., Sato S., Asamizu E., Kato T., Sasamoto S.,
RA Watanabe A., Idesawa K., Ishikawa A., Kawashima K., Kimura T., Kishida Y.,
RA Kiyokawa C., Kohara M., Matsumoto M., Matsuno A., Mochizuki Y.,
RA Nakayama S., Nakazaki N., Shimpo S., Sugimoto M., Takeuchi C., Yamada M.,
RA Tabata S.;
RT "Complete genome structure of the nitrogen-fixing symbiotic bacterium
RT Mesorhizobium loti.";
RL DNA Res. 7:331-338(2000).
RN [2]
RP FUNCTION, CATALYTIC ACTIVITY, COFACTOR, ACTIVITY REGULATION,
RP BIOPHYSICOCHEMICAL PROPERTIES, AND BIOTECHNOLOGY.
RC STRAIN=LMG 29417 / CECT 9101 / MAFF 303099;
RX PubMed=19133227; DOI=10.1016/j.bbrc.2008.12.158;
RA Hara R., Kino K.;
RT "Characterization of novel 2-oxoglutarate dependent dioxygenases converting
RT L-proline to cis-4-hydroxy-l-proline.";
RL Biochem. Biophys. Res. Commun. 379:882-886(2009).
CC -!- FUNCTION: Dioxygenase that catalyzes the 2-oxoglutarate-dependent
CC selective hydroxylation of free L-proline to cis-4-hydroxy-L-proline
CC (cis-4-Hyp). {ECO:0000269|PubMed:19133227}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=2-oxoglutarate + L-proline + O2 = cis-4-hydroxy-L-proline +
CC CO2 + succinate; Xref=Rhea:RHEA:32127, ChEBI:CHEBI:15379,
CC ChEBI:CHEBI:16526, ChEBI:CHEBI:16810, ChEBI:CHEBI:30031,
CC ChEBI:CHEBI:60039, ChEBI:CHEBI:63727; EC=1.14.11.56;
CC Evidence={ECO:0000269|PubMed:19133227};
CC -!- COFACTOR:
CC Name=Fe(2+); Xref=ChEBI:CHEBI:29033;
CC Evidence={ECO:0000269|PubMed:19133227};
CC Note=Binds 1 Fe(2+) ion. {ECO:0000269|PubMed:19133227};
CC -!- ACTIVITY REGULATION: Inhibited by metal ions such as Co(2+), Zn(2+),
CC Cu(2+) or Ni(2+). Is also inhibited by EDTA or diethylpyrocarbonate
CC (DEPC) in vitro. Unlike the procollagen-proline cis-3- and trans-4-
CC hydroxylases from mammals, does not necessarily require L-ascorbate for
CC activity although it does increase the activity of the enzyme.
CC {ECO:0000269|PubMed:19133227}.
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=0.54 mM for L-proline {ECO:0000269|PubMed:19133227};
CC KM=0.25 mM for 2-oxoglutarate {ECO:0000269|PubMed:19133227};
CC Note=kcat is 24 sec(-1).;
CC pH dependence:
CC Optimum pH is 6.5. {ECO:0000269|PubMed:19133227};
CC Temperature dependence:
CC Optimum temperature is 25 degrees Celsius.
CC {ECO:0000269|PubMed:19133227};
CC -!- BIOTECHNOLOGY: Would be one of the most promising biocatalysts for
CC production of cis-4-hydroxy-L-proline (cis-4-Hyp), a compound which was
CC clinically evaluated as an anticancer drug.
CC {ECO:0000269|PubMed:19133227}.
CC -!- SIMILARITY: Belongs to the L-proline cis-4-/cis-3-hydroxylase family.
CC {ECO:0000305}.
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DR EMBL; BA000012; BAB52605.1; -; Genomic_DNA.
DR RefSeq; WP_010913924.1; NC_002678.2.
DR PDB; 4P7W; X-ray; 1.80 A; A=2-280.
DR PDB; 4P7X; X-ray; 1.30 A; A=2-280.
DR PDBsum; 4P7W; -.
DR PDBsum; 4P7X; -.
DR AlphaFoldDB; Q989T9; -.
DR SMR; Q989T9; -.
DR EnsemblBacteria; BAB52605; BAB52605; BAB52605.
DR KEGG; mlo:mlr6283; -.
DR PATRIC; fig|266835.9.peg.4992; -.
DR eggNOG; COG3555; Bacteria.
DR HOGENOM; CLU_962849_0_0_5; -.
DR OMA; EIWFLDA; -.
DR OrthoDB; 1564693at2; -.
DR BRENDA; 1.14.11.56; 3243.
DR Proteomes; UP000000552; Chromosome.
DR GO; GO:0016706; F:2-oxoglutarate-dependent dioxygenase activity; IEA:InterPro.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0018193; P:peptidyl-amino acid modification; IEA:InterPro.
DR Gene3D; 1.10.1720.10; -; 1.
DR Gene3D; 2.60.120.330; -; 1.
DR InterPro; IPR007803; Asp/Arg/Pro-Hydrxlase.
DR InterPro; IPR027443; IPNS-like_sf.
DR InterPro; IPR008035; Pro_3_hydrox_C.
DR InterPro; IPR037037; Pro_3_hydrox_C_sf.
DR Pfam; PF05118; Asp_Arg_Hydrox; 1.
DR Pfam; PF05373; Pro_3_hydrox_C; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Dioxygenase; Iron; Metal-binding; Oxidoreductase.
FT CHAIN 1..280
FT /note="L-proline cis-4-hydroxylase"
FT /id="PRO_0000393424"
FT BINDING 106
FT /ligand="Fe cation"
FT /ligand_id="ChEBI:CHEBI:24875"
FT /evidence="ECO:0000250"
FT BINDING 108
FT /ligand="Fe cation"
FT /ligand_id="ChEBI:CHEBI:24875"
FT /evidence="ECO:0000250"
FT BINDING 154
FT /ligand="Fe cation"
FT /ligand_id="ChEBI:CHEBI:24875"
FT /evidence="ECO:0000250"
FT BINDING 164
FT /ligand="2-oxoglutarate"
FT /ligand_id="ChEBI:CHEBI:16810"
FT /evidence="ECO:0000255"
FT STRAND 4..8
FT /evidence="ECO:0007829|PDB:4P7X"
FT HELIX 13..23
FT /evidence="ECO:0007829|PDB:4P7X"
FT HELIX 33..35
FT /evidence="ECO:0007829|PDB:4P7X"
FT STRAND 36..50
FT /evidence="ECO:0007829|PDB:4P7X"
FT HELIX 68..71
FT /evidence="ECO:0007829|PDB:4P7X"
FT HELIX 74..83
FT /evidence="ECO:0007829|PDB:4P7X"
FT HELIX 86..88
FT /evidence="ECO:0007829|PDB:4P7X"
FT STRAND 89..97
FT /evidence="ECO:0007829|PDB:4P7X"
FT STRAND 101..106
FT /evidence="ECO:0007829|PDB:4P7X"
FT STRAND 112..114
FT /evidence="ECO:0007829|PDB:4P7X"
FT STRAND 116..124
FT /evidence="ECO:0007829|PDB:4P7X"
FT STRAND 129..133
FT /evidence="ECO:0007829|PDB:4P7X"
FT STRAND 136..138
FT /evidence="ECO:0007829|PDB:4P7X"
FT STRAND 144..148
FT /evidence="ECO:0007829|PDB:4P7X"
FT STRAND 154..158
FT /evidence="ECO:0007829|PDB:4P7X"
FT STRAND 160..162
FT /evidence="ECO:0007829|PDB:4P7X"
FT STRAND 164..172
FT /evidence="ECO:0007829|PDB:4P7X"
FT HELIX 177..179
FT /evidence="ECO:0007829|PDB:4P7X"
FT HELIX 202..209
FT /evidence="ECO:0007829|PDB:4P7X"
FT HELIX 210..213
FT /evidence="ECO:0007829|PDB:4P7X"
FT TURN 217..219
FT /evidence="ECO:0007829|PDB:4P7X"
FT HELIX 220..229
FT /evidence="ECO:0007829|PDB:4P7X"
FT HELIX 230..232
FT /evidence="ECO:0007829|PDB:4P7X"
FT STRAND 234..236
FT /evidence="ECO:0007829|PDB:4P7X"
FT HELIX 240..252
FT /evidence="ECO:0007829|PDB:4P7X"
FT HELIX 255..269
FT /evidence="ECO:0007829|PDB:4P7X"
SQ SEQUENCE 280 AA; 32217 MW; 693FD11F81AD47FE CRC64;
MTTRILGVVQ LDQRRLTDDL AVLAKSNFSS EYSDFACGRW EFCMLRNQSG KQEEQRVVVH
ETPALATPLG QSLPYLNELL DNHFDRDSIR YARIIRISEN ACIIPHRDYL ELEGKFIRVH
LVLDTNEKCS NTEENNIFHM GRGEIWFLDA SLPHSAGCFS PTPRLHLVVD IEGTRSLEEV
AINVEQPSAR NATVDTRKEW TDETLESVLG FSEIISEANY REIVAILAKL HFFHKVHCVD
MYGWLKEICR RRGEPALIEK ANSLERFYLI DRAAGEVMTY
