CDTS_MYCTU
ID CDTS_MYCTU Reviewed; 289 AA.
AC P9WPF9; Q50688; Q7D7C6;
DT 16-APR-2014, integrated into UniProtKB/Swiss-Prot.
DT 16-APR-2014, sequence version 1.
DT 03-AUG-2022, entry version 37.
DE RecName: Full=Cyclo(L-tyrosyl-L-tyrosyl) synthase;
DE EC=2.3.2.21;
DE AltName: Full=Cyclodipeptide synthase;
DE Short=CDPS;
DE AltName: Full=Cyclodityrosine synthase;
GN OrderedLocusNames=Rv2275;
OS Mycobacterium tuberculosis (strain ATCC 25618 / H37Rv).
OC Bacteria; Actinobacteria; Corynebacteriales; Mycobacteriaceae;
OC Mycobacterium; Mycobacterium tuberculosis complex.
OX NCBI_TaxID=83332;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=ATCC 25618 / H37Rv;
RX PubMed=9634230; DOI=10.1038/31159;
RA Cole S.T., Brosch R., Parkhill J., Garnier T., Churcher C.M., Harris D.E.,
RA Gordon S.V., Eiglmeier K., Gas S., Barry C.E. III, Tekaia F., Badcock K.,
RA Basham D., Brown D., Chillingworth T., Connor R., Davies R.M., Devlin K.,
RA Feltwell T., Gentles S., Hamlin N., Holroyd S., Hornsby T., Jagels K.,
RA Krogh A., McLean J., Moule S., Murphy L.D., Oliver S., Osborne J.,
RA Quail M.A., Rajandream M.A., Rogers J., Rutter S., Seeger K., Skelton S.,
RA Squares S., Squares R., Sulston J.E., Taylor K., Whitehead S.,
RA Barrell B.G.;
RT "Deciphering the biology of Mycobacterium tuberculosis from the complete
RT genome sequence.";
RL Nature 393:537-544(1998).
RN [2]
RP FUNCTION, CATALYTIC ACTIVITY, AND SUBSTRATE SPECIFICITY.
RX PubMed=19430487; DOI=10.1038/nchembio.175;
RA Gondry M., Sauguet L., Belin P., Thai R., Amouroux R., Tellier C.,
RA Tuphile K., Jacquet M., Braud S., Courcon M., Masson C., Dubois S.,
RA Lautru S., Lecoq A., Hashimoto S., Genet R., Pernodet J.L.;
RT "Cyclodipeptide synthases arec a family of tRNA-dependent peptide bond-
RT forming enzymes.";
RL Nat. Chem. Biol. 5:414-420(2009).
RN [3]
RP X-RAY CRYSTALLOGRAPHY (2.02 ANGSTROMS), MUTAGENESIS OF SER-88; TYR-229;
RP GLU-233 AND TYR-253, ACTIVE SITE, BIOPHYSICOCHEMICAL PROPERTIES, REACTION
RP MECHANISM, AND SUBUNIT.
RX PubMed=20852636; DOI=10.1038/nchembio.440;
RA Vetting M.W., Hegde S.S., Blanchard J.S.;
RT "The structure and mechanism of the Mycobacterium tuberculosis
RT cyclodityrosine synthetase.";
RL Nat. Chem. Biol. 6:797-799(2010).
CC -!- FUNCTION: Involved in the biosynthesis of mycocyclosin. It uses
CC activated amino acids in the form of aminoacyl-tRNAs (aa-tRNAs) as
CC substrates to catalyze the ATP-independent formation of cyclodipeptides
CC which are intermediates in diketopiperazine (DKP) biosynthetic
CC pathways. Catalyzes the formation of cyclo(L-Tyr-L-Tyr) (cYY) from L-
CC tyrosyl-tRNA(Tyr). Can incorporate various nonpolar residues, such as
CC L-phenylalanine, L-leucine, L-tyrosine and L-methionine, and to a much
CC lesser extent L-alanine, into cyclodipeptides. Cyclodipeptides
CC synthesized by Rv2275 always contain L-tyrosine.
CC {ECO:0000269|PubMed:19430487}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=2 L-tyrosyl-tRNA(Tyr) = cyclo(L-tyrosyl-L-tyrosyl) + 2
CC tRNA(Tyr); Xref=Rhea:RHEA:46448, Rhea:RHEA-COMP:9706, Rhea:RHEA-
CC COMP:9707, ChEBI:CHEBI:65063, ChEBI:CHEBI:78442, ChEBI:CHEBI:78536;
CC EC=2.3.2.21; Evidence={ECO:0000269|PubMed:19430487};
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=3.6 uM for L-tyrosyl-tRNA(Tyr) {ECO:0000269|PubMed:20852636};
CC -!- SUBUNIT: Homodimer. {ECO:0000269|PubMed:20852636}.
CC -!- MISCELLANEOUS: The reaction proceeds following a ping-pong mechanism
CC forming a covalent intermediate between an active site Ser-88 and the
CC L-phenylalanine residue. {ECO:0000305|PubMed:20852636}.
CC -!- SIMILARITY: Belongs to the CDPS family. {ECO:0000305}.
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DR EMBL; AL123456; CCP45057.1; -; Genomic_DNA.
DR PIR; G70730; G70730.
DR RefSeq; NP_216791.1; NC_000962.3.
DR RefSeq; WP_003411681.1; NZ_NVQJ01000008.1.
DR PDB; 2X9Q; X-ray; 2.02 A; A/B=1-289.
DR PDBsum; 2X9Q; -.
DR AlphaFoldDB; P9WPF9; -.
DR SMR; P9WPF9; -.
DR STRING; 83332.Rv2275; -.
DR PaxDb; P9WPF9; -.
DR DNASU; 888355; -.
DR GeneID; 888355; -.
DR KEGG; mtu:Rv2275; -.
DR TubercuList; Rv2275; -.
DR eggNOG; ENOG5033PIU; Bacteria.
DR OMA; LAYHRPW; -.
DR BioCyc; MetaCyc:G185E-6493-MON; -.
DR BRENDA; 2.3.2.21; 3445.
DR SABIO-RK; P9WPF9; -.
DR Proteomes; UP000001584; Chromosome.
DR GO; GO:0016755; F:aminoacyltransferase activity; IDA:UniProtKB.
DR GO; GO:0016875; F:ligase activity, forming carbon-oxygen bonds; IDA:MTBBASE.
DR Gene3D; 3.40.50.11710; -; 1.
DR InterPro; IPR030903; CDPS.
DR InterPro; IPR038622; CDPS_sf.
DR Pfam; PF16715; CDPS; 1.
DR TIGRFAMs; TIGR04539; tRNA_cyclodipep; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Reference proteome; Transferase.
FT CHAIN 1..289
FT /note="Cyclo(L-tyrosyl-L-tyrosyl) synthase"
FT /id="PRO_0000423356"
FT REGION 1..48
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT ACT_SITE 88
FT /note="Nucleophile"
FT /evidence="ECO:0000305|PubMed:20852636"
FT BINDING 91
FT /ligand="substrate"
FT /evidence="ECO:0000250"
FT BINDING 229..233
FT /ligand="substrate"
FT /evidence="ECO:0000250"
FT BINDING 253
FT /ligand="substrate"
FT /evidence="ECO:0000250"
FT SITE 91
FT /note="Could have a critical role in the catalytic
FT mechanism"
FT /evidence="ECO:0000250"
FT SITE 139
FT /note="Could be involved in aa-tRNA binding"
FT /evidence="ECO:0000250"
FT SITE 229
FT /note="Could be involved in aa-tRNA binding"
FT /evidence="ECO:0000250"
FT SITE 233
FT /note="Could have a critical role in the catalytic
FT mechanism"
FT /evidence="ECO:0000250"
FT MUTAGEN 88
FT /note="S->A: Complete loss of cYY-forming activity."
FT /evidence="ECO:0000269|PubMed:20852636"
FT MUTAGEN 229
FT /note="Y->F: Small but detectable amount of cYY-forming
FT activity."
FT /evidence="ECO:0000269|PubMed:20852636"
FT MUTAGEN 233
FT /note="E->A: Complete loss of cYY-forming activity."
FT /evidence="ECO:0000269|PubMed:20852636"
FT MUTAGEN 233
FT /note="E->Q: Complete loss of cYY-forming activity."
FT /evidence="ECO:0000269|PubMed:20852636"
FT MUTAGEN 253
FT /note="Y->F: Small but detectable amount of catalytic
FT activity (200-fold decrease)."
FT /evidence="ECO:0000269|PubMed:20852636"
FT STRAND 52..54
FT /evidence="ECO:0007829|PDB:2X9Q"
FT STRAND 59..61
FT /evidence="ECO:0007829|PDB:2X9Q"
FT STRAND 64..70
FT /evidence="ECO:0007829|PDB:2X9Q"
FT HELIX 71..79
FT /evidence="ECO:0007829|PDB:2X9Q"
FT STRAND 82..87
FT /evidence="ECO:0007829|PDB:2X9Q"
FT HELIX 96..109
FT /evidence="ECO:0007829|PDB:2X9Q"
FT STRAND 111..117
FT /evidence="ECO:0007829|PDB:2X9Q"
FT HELIX 122..128
FT /evidence="ECO:0007829|PDB:2X9Q"
FT HELIX 133..158
FT /evidence="ECO:0007829|PDB:2X9Q"
FT STRAND 163..169
FT /evidence="ECO:0007829|PDB:2X9Q"
FT HELIX 170..175
FT /evidence="ECO:0007829|PDB:2X9Q"
FT HELIX 177..192
FT /evidence="ECO:0007829|PDB:2X9Q"
FT HELIX 194..210
FT /evidence="ECO:0007829|PDB:2X9Q"
FT HELIX 220..244
FT /evidence="ECO:0007829|PDB:2X9Q"
FT STRAND 249..255
FT /evidence="ECO:0007829|PDB:2X9Q"
FT HELIX 260..263
FT /evidence="ECO:0007829|PDB:2X9Q"
FT STRAND 266..270
FT /evidence="ECO:0007829|PDB:2X9Q"
FT STRAND 276..283
FT /evidence="ECO:0007829|PDB:2X9Q"
SQ SEQUENCE 289 AA; 31612 MW; D0B98859EE8CEF38 CRC64;
MSYVAAEPGV LISPTDDLQS PRSAPAAHDE NADGITGGTR DDSAPNSRFQ LGRRIPEATA
QEGFLVRPFT QQCQIIHTEG DHAVIGVSPG NSYFSRQRLR DLGLWGLTNF DRVDFVYTDV
HVAESYEALG DSAIEARRKA VKNIRGVRAK ITTTVNELDP AGARLCVRPM SEFQSNEAYR
ELHADLLTRL KDDEDLRAVC QDLVRRFLST KVGPRQGATA TQEQVCMDYI CAEAPLFLDT
PAILGVPSSL NCYHQSLPLA EMLYARGSGL RASRNQGHAI VTPDGSPAE
