CMLA_STRVP
ID CMLA_STRVP Reviewed; 532 AA.
AC F2RB80;
DT 08-MAY-2019, integrated into UniProtKB/Swiss-Prot.
DT 31-MAY-2011, sequence version 1.
DT 03-AUG-2022, entry version 65.
DE RecName: Full=4-amino-L-phenylalanyl-[CmlP-peptidyl-carrier-protein] 3-hydroxylase {ECO:0000305};
DE EC=1.14.99.65 {ECO:0000269|PubMed:20713732};
GN Name=cmlA {ECO:0000303|PubMed:20713732};
GN OrderedLocusNames=SVEN_0921 {ECO:0000312|EMBL:CCA54208.1};
OS Streptomyces venezuelae (strain ATCC 10712 / CBS 650.69 / DSM 40230 / JCM
OS 4526 / NBRC 13096 / PD 04745).
OC Bacteria; Actinobacteria; Streptomycetales; Streptomycetaceae;
OC Streptomyces.
OX NCBI_TaxID=953739;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=ATCC 10712 / CBS 650.69 / DSM 40230 / JCM 4526 / NBRC 13096 / PD
RC 04745;
RX PubMed=21463507; DOI=10.1186/1471-2164-12-175;
RA Pullan S.T., Chandra G., Bibb M.J., Merrick M.;
RT "Genome-wide analysis of the role of GlnR in Streptomyces venezuelae
RT provides new insights into global nitrogen regulation in actinomycetes.";
RL BMC Genomics 12:175-175(2011).
RN [2]
RP FUNCTION, CATALYTIC ACTIVITY, COFACTOR, AND PATHWAY.
RX PubMed=20713732; DOI=10.1073/pnas.1007953107;
RA Makris T.M., Chakrabarti M., Muenck E., Lipscomb J.D.;
RT "A family of diiron monooxygenases catalyzing amino acid beta-hydroxylation
RT in antibiotic biosynthesis.";
RL Proc. Natl. Acad. Sci. U.S.A. 107:15391-15396(2010).
RN [3] {ECO:0007744|PDB:4JO0}
RP X-RAY CRYSTALLOGRAPHY (2.17 ANGSTROMS) IN COMPLEX WITH IRON, COFACTOR,
RP SUBUNIT, AND MUTAGENESIS OF GLU-430.
RX PubMed=23980641; DOI=10.1021/bi400845b;
RA Makris T.M., Knoot C.J., Wilmot C.M., Lipscomb J.D.;
RT "Structure of a dinuclear iron cluster-containing beta-hydroxylase active
RT in antibiotic biosynthesis.";
RL Biochemistry 52:6662-6671(2013).
RN [4] {ECO:0007744|PDB:5KIK, ECO:0007744|PDB:5KIL}
RP X-RAY CRYSTALLOGRAPHY (2.20 ANGSTROMS) OF WILD-TYPE AND MUTANT ASP-377 IN
RP COMPLEXES WITH IRON, COFACTOR, AND MUTAGENESIS OF GLU-377.
RX PubMed=27668828; DOI=10.1021/acs.biochem.6b00834;
RA Jasniewski A.J., Knoot C.J., Lipscomb J.D., Que L.;
RT "A carboxylate shift regulates dioxygen activation by the diiron nonheme
RT beta-hydroxylase CmlA upon binding of a substrate-loaded nonribosomal
RT peptide synthetase.";
RL Biochemistry 55:5818-5831(2016).
CC -!- FUNCTION: Involved in chloramphenicol biosynthesis (PubMed:20713732).
CC Catalyzes the beta-hydroxylation of 4-amino-L-phenylalanine (L-PAPA)
CC covalently bound to CmlP to form L-p-aminophenylserine
CC (PubMed:20713732). {ECO:0000269|PubMed:20713732}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=4-amino-L-phenylalanyl-[peptidyl-carrier protein] + AH2 + O2 =
CC (2R)-2-(4-aminophenyl)-L-seryl-[peptidyl-carrier protein] + A + H2O;
CC Xref=Rhea:RHEA:22684, Rhea:RHEA-COMP:15237, Rhea:RHEA-COMP:15238,
CC ChEBI:CHEBI:13193, ChEBI:CHEBI:15377, ChEBI:CHEBI:15379,
CC ChEBI:CHEBI:17499, ChEBI:CHEBI:142855, ChEBI:CHEBI:142857;
CC EC=1.14.99.65; Evidence={ECO:0000269|PubMed:20713732};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:22685;
CC Evidence={ECO:0000269|PubMed:20713732};
CC -!- COFACTOR:
CC Name=Fe(2+); Xref=ChEBI:CHEBI:29033;
CC Evidence={ECO:0000269|PubMed:20713732, ECO:0000269|PubMed:23980641,
CC ECO:0000269|PubMed:27668828};
CC Note=Contains a dinuclear iron cluster that becomes oxo-bridged (Fe-O-
CC Fe) during O(2) activation. {ECO:0000269|PubMed:23980641,
CC ECO:0000269|PubMed:27668828};
CC -!- PATHWAY: Antibiotic biosynthesis. {ECO:0000269|PubMed:20713732}.
CC -!- SUBUNIT: Homodimer. {ECO:0000269|PubMed:23980641}.
CC -!- SIMILARITY: Belongs to the metallo-beta-lactamase superfamily.
CC {ECO:0000305}.
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DR EMBL; FR845719; CCA54208.1; -; Genomic_DNA.
DR RefSeq; WP_015032127.1; NZ_CP029197.1.
DR PDB; 4JO0; X-ray; 2.17 A; A=1-532.
DR PDB; 5KIK; X-ray; 2.20 A; A=1-532.
DR PDB; 5KIL; X-ray; 2.72 A; A=1-532.
DR PDBsum; 4JO0; -.
DR PDBsum; 5KIK; -.
DR PDBsum; 5KIL; -.
DR AlphaFoldDB; F2RB80; -.
DR SMR; F2RB80; -.
DR STRING; 953739.SVEN_0921; -.
DR EnsemblBacteria; CCA54208; CCA54208; SVEN_0921.
DR KEGG; sve:SVEN_0921; -.
DR PATRIC; fig|953739.5.peg.2967; -.
DR eggNOG; COG2220; Bacteria.
DR HOGENOM; CLU_516704_0_0_11; -.
DR OMA; PKMLGGP; -.
DR BioCyc; MetaCyc:MON-20704; -.
DR BRENDA; 1.14.99.65; 6106.
DR Proteomes; UP000006854; Chromosome.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0016491; F:oxidoreductase activity; IEA:UniProtKB-KW.
DR GO; GO:0017000; P:antibiotic biosynthetic process; IEA:UniProtKB-KW.
DR Gene3D; 3.60.15.10; -; 1.
DR InterPro; IPR041141; CmlA_N.
DR InterPro; IPR001279; Metallo-B-lactamas.
DR InterPro; IPR036866; RibonucZ/Hydroxyglut_hydro.
DR Pfam; PF18456; CmlA_N; 1.
DR Pfam; PF12706; Lactamase_B_2; 1.
DR SUPFAM; SSF56281; SSF56281; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Antibiotic biosynthesis; Iron; Metal-binding; Oxidoreductase;
KW Reference proteome.
FT CHAIN 1..532
FT /note="4-amino-L-phenylalanyl-[CmlP-peptidyl-carrier-
FT protein] 3-hydroxylase"
FT /id="PRO_0000447246"
FT BINDING 305
FT /ligand="Fe cation"
FT /ligand_id="ChEBI:CHEBI:24875"
FT /ligand_label="1"
FT /evidence="ECO:0000269|PubMed:23980641,
FT ECO:0000269|PubMed:27668828"
FT BINDING 307
FT /ligand="Fe cation"
FT /ligand_id="ChEBI:CHEBI:24875"
FT /ligand_label="1"
FT /evidence="ECO:0000269|PubMed:23980641,
FT ECO:0000269|PubMed:27668828"
FT BINDING 309
FT /ligand="Fe cation"
FT /ligand_id="ChEBI:CHEBI:24875"
FT /ligand_label="2"
FT /evidence="ECO:0000269|PubMed:23980641,
FT ECO:0000269|PubMed:27668828"
FT BINDING 310
FT /ligand="Fe cation"
FT /ligand_id="ChEBI:CHEBI:24875"
FT /ligand_label="2"
FT /evidence="ECO:0000269|PubMed:23980641,
FT ECO:0000269|PubMed:27668828"
FT BINDING 377
FT /ligand="Fe cation"
FT /ligand_id="ChEBI:CHEBI:24875"
FT /ligand_label="1"
FT /evidence="ECO:0000269|PubMed:23980641,
FT ECO:0000269|PubMed:27668828"
FT BINDING 403
FT /ligand="Fe cation"
FT /ligand_id="ChEBI:CHEBI:24875"
FT /ligand_label="1"
FT /evidence="ECO:0000269|PubMed:23980641,
FT ECO:0000269|PubMed:27668828"
FT BINDING 403
FT /ligand="Fe cation"
FT /ligand_id="ChEBI:CHEBI:24875"
FT /ligand_label="2"
FT /evidence="ECO:0000269|PubMed:23980641,
FT ECO:0000269|PubMed:27668828"
FT MUTAGEN 377
FT /note="E->D: Unable to generate the hydroxylated product."
FT /evidence="ECO:0000269|PubMed:27668828"
FT MUTAGEN 430
FT /note="E->A: Decrease in activity. Interacts strongly with
FT the diiron cluster."
FT /evidence="ECO:0000269|PubMed:23980641"
FT STRAND 3..5
FT /evidence="ECO:0007829|PDB:4JO0"
FT STRAND 9..15
FT /evidence="ECO:0007829|PDB:4JO0"
FT HELIX 22..24
FT /evidence="ECO:0007829|PDB:4JO0"
FT HELIX 27..36
FT /evidence="ECO:0007829|PDB:4JO0"
FT HELIX 38..47
FT /evidence="ECO:0007829|PDB:4JO0"
FT HELIX 49..56
FT /evidence="ECO:0007829|PDB:4JO0"
FT HELIX 59..61
FT /evidence="ECO:0007829|PDB:4JO0"
FT HELIX 70..72
FT /evidence="ECO:0007829|PDB:4JO0"
FT HELIX 73..82
FT /evidence="ECO:0007829|PDB:4JO0"
FT HELIX 84..102
FT /evidence="ECO:0007829|PDB:4JO0"
FT HELIX 105..107
FT /evidence="ECO:0007829|PDB:4JO0"
FT STRAND 109..111
FT /evidence="ECO:0007829|PDB:4JO0"
FT HELIX 114..118
FT /evidence="ECO:0007829|PDB:4JO0"
FT TURN 122..126
FT /evidence="ECO:0007829|PDB:4JO0"
FT STRAND 127..132
FT /evidence="ECO:0007829|PDB:4JO0"
FT STRAND 136..143
FT /evidence="ECO:0007829|PDB:4JO0"
FT HELIX 145..150
FT /evidence="ECO:0007829|PDB:4JO0"
FT HELIX 156..158
FT /evidence="ECO:0007829|PDB:4JO0"
FT STRAND 159..165
FT /evidence="ECO:0007829|PDB:4JO0"
FT STRAND 187..190
FT /evidence="ECO:0007829|PDB:4JO0"
FT HELIX 196..203
FT /evidence="ECO:0007829|PDB:4JO0"
FT HELIX 208..217
FT /evidence="ECO:0007829|PDB:4JO0"
FT HELIX 222..229
FT /evidence="ECO:0007829|PDB:4JO0"
FT STRAND 232..234
FT /evidence="ECO:0007829|PDB:4JO0"
FT STRAND 252..257
FT /evidence="ECO:0007829|PDB:4JO0"
FT STRAND 260..265
FT /evidence="ECO:0007829|PDB:4JO0"
FT STRAND 268..273
FT /evidence="ECO:0007829|PDB:4JO0"
FT HELIX 291..293
FT /evidence="ECO:0007829|PDB:4JO0"
FT STRAND 298..302
FT /evidence="ECO:0007829|PDB:4JO0"
FT STRAND 305..307
FT /evidence="ECO:0007829|PDB:5KIL"
FT TURN 308..310
FT /evidence="ECO:0007829|PDB:4JO0"
FT HELIX 313..319
FT /evidence="ECO:0007829|PDB:4JO0"
FT HELIX 320..322
FT /evidence="ECO:0007829|PDB:4JO0"
FT STRAND 323..329
FT /evidence="ECO:0007829|PDB:4JO0"
FT STRAND 335..338
FT /evidence="ECO:0007829|PDB:4JO0"
FT HELIX 341..347
FT /evidence="ECO:0007829|PDB:4JO0"
FT STRAND 353..356
FT /evidence="ECO:0007829|PDB:4JO0"
FT STRAND 361..364
FT /evidence="ECO:0007829|PDB:4JO0"
FT STRAND 367..373
FT /evidence="ECO:0007829|PDB:4JO0"
FT STRAND 386..393
FT /evidence="ECO:0007829|PDB:4JO0"
FT STRAND 396..400
FT /evidence="ECO:0007829|PDB:4JO0"
FT HELIX 411..419
FT /evidence="ECO:0007829|PDB:4JO0"
FT STRAND 423..428
FT /evidence="ECO:0007829|PDB:4JO0"
FT HELIX 436..440
FT /evidence="ECO:0007829|PDB:4JO0"
FT HELIX 441..443
FT /evidence="ECO:0007829|PDB:4JO0"
FT STRAND 444..446
FT /evidence="ECO:0007829|PDB:4JO0"
FT HELIX 450..455
FT /evidence="ECO:0007829|PDB:4JO0"
FT HELIX 463..473
FT /evidence="ECO:0007829|PDB:4JO0"
FT STRAND 476..481
FT /evidence="ECO:0007829|PDB:4JO0"
FT HELIX 487..491
FT /evidence="ECO:0007829|PDB:4JO0"
FT HELIX 502..516
FT /evidence="ECO:0007829|PDB:4JO0"
FT STRAND 520..523
FT /evidence="ECO:0007829|PDB:4JO0"
FT STRAND 528..530
FT /evidence="ECO:0007829|PDB:4JO0"
SQ SEQUENCE 532 AA; 60171 MW; 34119BB7AAB0B078 CRC64;
MRYSLRQDIA VEPVIAGWYG WSYLLPPQTL ARFVHNRFNR IVESYLDDPQ VHAAAVRQRR
MHGGPWIHAH EHRDAIEAWY RETAPRRERL DELFEAVRRL EEDILPRHHG ECLDPVYQEL
PAALAGRVEV FYGRDNRTAD YRFVEPLMYA SEYYDESWQQ VRFRPVTEDA REFALTTPML
EYGPEQLLVD VPLNSPLLDA VFRGGLTGTE LDDLAARFGL DGERAARFAS YFEPTPAASE
APAPASSSEE DVLEYVGHAC VFARHRGTTF LVDPVLSYSG YPGGAENRFT FADLPERIDH
LLITHNHQDH MLFETLLRIR HRVGRVLVPK STNASLVDPG LGGILRRLGF TDVVEVDDLE
TLSCGSAEVV ALPFLGEHGD LRIRSKTGWL IRFGERSVLF AADSTNISPT MYTKVAEVIG
PVDTVFIGME SIGAAASWIY GPLYGEPLDR RTDQSRRLNG SNFPQAREIV DALEPDEVYV
YAMGLEPWMG VVMAVDYDES HPAIVDSDLL VRHVQDKGGT AERLHLRRTL RL
