CDLS_BACLD
ID CDLS_BACLD Reviewed; 249 AA.
AC Q65EX3; Q62QE0;
DT 18-SEP-2013, integrated into UniProtKB/Swiss-Prot.
DT 25-OCT-2004, sequence version 1.
DT 03-AUG-2022, entry version 87.
DE RecName: Full=Cyclo(L-leucyl-L-leucyl) synthase;
DE EC=2.3.2.22;
DE AltName: Full=Cyclodileucine synthase;
DE AltName: Full=Cyclodipeptide synthase;
DE Short=CDPS;
GN Name=yvmC; OrderedLocusNames=BL00817, BLi03566;
OS Bacillus licheniformis (strain ATCC 14580 / DSM 13 / JCM 2505 / CCUG 7422 /
OS NBRC 12200 / NCIMB 9375 / NCTC 10341 / NRRL NRS-1264 / Gibson 46).
OC Bacteria; Firmicutes; Bacilli; Bacillales; Bacillaceae; Bacillus.
OX NCBI_TaxID=279010;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=ATCC 14580 / DSM 13 / JCM 2505 / CCUG 7422 / NBRC 12200 / NCIMB 9375
RC / NCTC 10341 / NRRL NRS-1264 / Gibson 46;
RX PubMed=15461803; DOI=10.1186/gb-2004-5-10-r77;
RA Rey M.W., Ramaiya P., Nelson B.A., Brody-Karpin S.D., Zaretsky E.J.,
RA Tang M., Lopez de Leon A., Xiang H., Gusti V., Clausen I.G., Olsen P.B.,
RA Rasmussen M.D., Andersen J.T., Joergensen P.L., Larsen T.S., Sorokin A.,
RA Bolotin A., Lapidus A., Galleron N., Ehrlich S.D., Berka R.M.;
RT "Complete genome sequence of the industrial bacterium Bacillus
RT licheniformis and comparisons with closely related Bacillus species.";
RL Genome Biol. 5:R77.1-R77.12(2004).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=ATCC 14580 / DSM 13 / JCM 2505 / CCUG 7422 / NBRC 12200 / NCIMB 9375
RC / NCTC 10341 / NRRL NRS-1264 / Gibson 46;
RX PubMed=15383718; DOI=10.1159/000079829;
RA Veith B., Herzberg C., Steckel S., Feesche J., Maurer K.H., Ehrenreich P.,
RA Baeumer S., Henne A., Liesegang H., Merkl R., Ehrenreich A., Gottschalk G.;
RT "The complete genome sequence of Bacillus licheniformis DSM13, an organism
RT with great industrial potential.";
RL J. Mol. Microbiol. Biotechnol. 7:204-211(2004).
RN [3]
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 [4]
RP X-RAY CRYSTALLOGRAPHY (1.70 ANGSTROMS) WITH SUBSTRATE ANALOGS, FUNCTION,
RP CATALYTIC ACTIVITY, SUBSTRATE SPECIFICITY, MUTAGENESIS OF SER-37; ASN-40;
RP LYS-88; ARG-98; ARG-158; TYR-180; GLU-184; TYR-204 AND HIS-205, ACTIVE
RP SITE, REACTION MECHANISM, AND SUBUNIT.
RX PubMed=21325056; DOI=10.1073/pnas.1019480108;
RA Bonnefond L., Arai T., Sakaguchi Y., Suzuki T., Ishitani R., Nureki O.;
RT "Structural basis for nonribosomal peptide synthesis by an aminoacyl-tRNA
RT synthetase paralog.";
RL Proc. Natl. Acad. Sci. U.S.A. 108:3912-3917(2011).
CC -!- FUNCTION: Involved in the biosynthesis of pulcherrimin, a red
CC extracellular pigment. It uses activated amino acids in the form of
CC aminoacyl-tRNAs (aa-tRNAs) as substrates to catalyze the ATP-
CC independent formation of cyclodipeptides which are intermediates in
CC diketopiperazine (DKP) biosynthetic pathways. Catalyzes the formation
CC of cyclo(L-Leu-L-Leu) (cLL) from L-leucyl-tRNA(Leu). Can also
CC incorporate various nonpolar residues, such as L-phenylalanine, L-
CC leucine and methionine, into cyclodipeptides.
CC {ECO:0000269|PubMed:19430487, ECO:0000269|PubMed:21325056}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=2 L-leucyl-tRNA(Leu) = cyclo(L-leucyl-L-leucyl) + 2 H(+) + 2
CC tRNA(Leu); Xref=Rhea:RHEA:46452, Rhea:RHEA-COMP:9613, Rhea:RHEA-
CC COMP:9622, ChEBI:CHEBI:15378, ChEBI:CHEBI:67269, ChEBI:CHEBI:78442,
CC ChEBI:CHEBI:78494; EC=2.3.2.22;
CC Evidence={ECO:0000269|PubMed:19430487, ECO:0000269|PubMed:21325056};
CC -!- SUBUNIT: Monomer. {ECO:0000269|PubMed:21325056}.
CC -!- SIMILARITY: Belongs to the CDPS family. {ECO:0000305}.
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DR EMBL; CP000002; AAU25020.1; -; Genomic_DNA.
DR EMBL; AE017333; AAU42391.1; -; Genomic_DNA.
DR RefSeq; WP_009329597.1; NC_006322.1.
DR PDB; 3OQH; X-ray; 1.90 A; A/B=1-249.
DR PDB; 3OQI; X-ray; 1.70 A; A/B=1-249.
DR PDB; 3OQJ; X-ray; 2.40 A; A/B=1-249.
DR PDB; 3S7T; X-ray; 2.81 A; A/B=1-249.
DR PDBsum; 3OQH; -.
DR PDBsum; 3OQI; -.
DR PDBsum; 3OQJ; -.
DR PDBsum; 3S7T; -.
DR AlphaFoldDB; Q65EX3; -.
DR SMR; Q65EX3; -.
DR STRING; 279010.BL00817; -.
DR EnsemblBacteria; AAU25020; AAU25020; BL00817.
DR KEGG; bld:BLi03566; -.
DR KEGG; bli:BL00817; -.
DR PATRIC; fig|279010.13.peg.3624; -.
DR eggNOG; ENOG50332PQ; Bacteria.
DR HOGENOM; CLU_084186_1_0_9; -.
DR OMA; LAYHRPW; -.
DR OrthoDB; 1802439at2; -.
DR BioCyc; BLIC279010:BLI_RS17555-MON; -.
DR BRENDA; 2.3.2.22; 669.
DR EvolutionaryTrace; Q65EX3; -.
DR Proteomes; UP000000606; Chromosome.
DR GO; GO:0016755; F:aminoacyltransferase activity; IDA:UniProtKB.
DR GO; GO:0046148; P:pigment biosynthetic process; IDA:UniProtKB.
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..249
FT /note="Cyclo(L-leucyl-L-leucyl) synthase"
FT /id="PRO_0000423351"
FT ACT_SITE 37
FT /note="Nucleophile"
FT /evidence="ECO:0000305|PubMed:21325056"
FT BINDING 40
FT /ligand="substrate"
FT BINDING 180..184
FT /ligand="substrate"
FT BINDING 204
FT /ligand="substrate"
FT BINDING 209..210
FT /ligand="substrate"
FT SITE 40
FT /note="Could have a critical role in the catalytic
FT mechanism"
FT SITE 88
FT /note="Could be involved in aa-tRNA binding"
FT SITE 98
FT /note="Could be involved in aa-tRNA binding"
FT SITE 180
FT /note="Could be involved in aa-tRNA binding"
FT SITE 184
FT /note="Could have a critical role in the catalytic
FT mechanism"
FT MUTAGEN 37
FT /note="S->A: It is able to bind L-leucyl-tRNA(Leu), but has
FT almost no cyclodileucine synthase activity."
FT /evidence="ECO:0000269|PubMed:21325056"
FT MUTAGEN 37
FT /note="S->C: Lack of intermediate formation."
FT /evidence="ECO:0000269|PubMed:21325056"
FT MUTAGEN 40
FT /note="N->D: It is able to bind L-leucyl-tRNA(Leu), but has
FT almost no cyclodileucine synthase activity."
FT /evidence="ECO:0000269|PubMed:21325056"
FT MUTAGEN 88
FT /note="K->A: Strong decrease of L-leucyl-tRNA(Leu) binding,
FT but moderate decrease in the cyclodileucine synthase
FT activity; when associated with A-98."
FT /evidence="ECO:0000269|PubMed:21325056"
FT MUTAGEN 98
FT /note="R->A: Strong decrease of L-leucyl-tRNA(Leu) binding,
FT but moderate decrease in the cyclodileucine synthase
FT activity; when associated with A-88."
FT /evidence="ECO:0000269|PubMed:21325056"
FT MUTAGEN 158
FT /note="R->A: Moderate decrease in the cyclodileucine
FT synthase activity."
FT /evidence="ECO:0000269|PubMed:21325056"
FT MUTAGEN 180
FT /note="Y->A: Moderate decrease in the cyclodileucine
FT synthase activity."
FT /evidence="ECO:0000269|PubMed:21325056"
FT MUTAGEN 180
FT /note="Y->F: Strong decrease of L-leucyl-tRNA(Leu)
FT binding."
FT /evidence="ECO:0000269|PubMed:21325056"
FT MUTAGEN 184
FT /note="E->A: It is able to bind L-leucyl-tRNA(Leu), but has
FT almost no cyclodileucine synthase activity."
FT /evidence="ECO:0000269|PubMed:21325056"
FT MUTAGEN 184
FT /note="E->Q: It is able to bind L-leucyl-tRNA(Leu), but has
FT almost no cyclodileucine synthase activity."
FT /evidence="ECO:0000269|PubMed:21325056"
FT MUTAGEN 204
FT /note="Y->A: Strong decrease in the cyclodileucine synthase
FT activity."
FT /evidence="ECO:0000269|PubMed:21325056"
FT MUTAGEN 204
FT /note="Y->F: Strong decrease in the cyclodileucine synthase
FT activity."
FT /evidence="ECO:0000269|PubMed:21325056"
FT MUTAGEN 205
FT /note="H->E: Strong decrease of L-leucyl-tRNA(Leu)
FT binding."
FT /evidence="ECO:0000269|PubMed:21325056"
FT STRAND 14..19
FT /evidence="ECO:0007829|PDB:3OQI"
FT HELIX 20..28
FT /evidence="ECO:0007829|PDB:3OQI"
FT STRAND 31..36
FT /evidence="ECO:0007829|PDB:3OQI"
FT HELIX 45..58
FT /evidence="ECO:0007829|PDB:3OQI"
FT STRAND 60..66
FT /evidence="ECO:0007829|PDB:3OQI"
FT HELIX 71..77
FT /evidence="ECO:0007829|PDB:3OQI"
FT HELIX 82..107
FT /evidence="ECO:0007829|PDB:3OQI"
FT STRAND 114..116
FT /evidence="ECO:0007829|PDB:3OQI"
FT TURN 117..122
FT /evidence="ECO:0007829|PDB:3OQI"
FT HELIX 124..139
FT /evidence="ECO:0007829|PDB:3OQI"
FT HELIX 141..161
FT /evidence="ECO:0007829|PDB:3OQI"
FT HELIX 171..195
FT /evidence="ECO:0007829|PDB:3OQI"
FT STRAND 200..206
FT /evidence="ECO:0007829|PDB:3OQI"
FT HELIX 209..215
FT /evidence="ECO:0007829|PDB:3OQI"
FT STRAND 227..233
FT /evidence="ECO:0007829|PDB:3OQI"
SQ SEQUENCE 249 AA; 28550 MW; 9E66BB41B7DFB2BF CRC64;
MTELIMESKH QLFKTETLTQ NCNEILKRRR HVLVGISPFN SRFSEDYIHR LIAWAVREFQ
SVSVLLAGKE AANLLEALGT PHGKAERKVR KEVSRNRRFA EKALEAHGGN PEDIHTFSDF
ANQTAYRNLR MEVEAAFFDQ THFRNACLEM SHAAILGRAR GTRMDVVEVS ADMLELAVEY
VIAELPFFIA APDILGVEET LLAYHRPWKL GEQISRNEFA VKMRPNQGYL MVSEADERVE
SKSMQEERV
