CLPS_STRNR
ID CLPS_STRNR Reviewed; 239 AA.
AC Q8GED7;
DT 18-SEP-2013, integrated into UniProtKB/Swiss-Prot.
DT 01-MAR-2003, sequence version 1.
DT 03-AUG-2022, entry version 45.
DE RecName: Full=Cyclo(L-leucyl-L-phenylalanyl) synthase;
DE EC=2.3.2.20;
DE AltName: Full=Cyclodipeptide synthase;
DE Short=CDPS;
GN Name=albC;
OS Streptomyces noursei.
OC Bacteria; Actinobacteria; Streptomycetales; Streptomycetaceae;
OC Streptomyces.
OX NCBI_TaxID=1971;
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], FUNCTION, AND NOMENCLATURE.
RC STRAIN=ATCC 11455 / DSM 40635 / JCM 4922 / NBRC 15452 / NCIMB 8593 / NRRL
RC B-1714;
RX PubMed=12498889; DOI=10.1016/s1074-5521(02)00285-5;
RA Lautru S., Gondry M., Genet R., Pernodet J.L.;
RT "The albonoursin gene cluster of S noursei biosynthesis of diketopiperazine
RT metabolites independent of nonribosomal peptide synthetases.";
RL Chem. Biol. 9:1355-1364(2002).
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 (1.90 ANGSTROMS) OF 2-239, MUTAGENESIS OF GLY-35;
RP SER-37; TYR-178; GLU-182; LEU-200 AND TYR-202, ACTIVE SITE, REACTION
RP MECHANISM, AND SUBUNIT.
RX PubMed=21296757; DOI=10.1093/nar/gkr027;
RA Sauguet L., Moutiez M., Li Y., Belin P., Seguin J., Le Du M.H., Thai R.,
RA Masson C., Fonvielle M., Pernodet J.L., Charbonnier J.B., Gondry M.;
RT "Cyclodipeptide synthases, a family of class-I aminoacyl-tRNA synthetase-
RT like enzymes involved in non-ribosomal peptide synthesis.";
RL Nucleic Acids Res. 39:4475-4489(2011).
CC -!- FUNCTION: Involved in the biosynthesis of albonoursin
CC (cyclo[(alpha,beta-dehydro-Phe)-(alpha,beta-dehydro-Leu)]), an
CC antibacterial peptide. 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-Phe-L-Leu) (cFL) as major products from L-L-phenylalanyl-
CC tRNA(Phe) and L-leucyl-tRNA(Leu). AlbC can also incorporate various
CC nonpolar residues, such as L-phenylalanine, L-leucine, L-tyrosine and
CC L-methionine, and to a much lesser extent L-alanine and L-valine, into
CC cyclodipeptides. Indeed, ten possible cyclodipeptides composed of L-
CC phenylalanine, L-leucine, L-tyrosine and L-methionine are all
CC synthesized to detectable amounts by AlbC.
CC {ECO:0000269|PubMed:12498889, ECO:0000269|PubMed:19430487}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=L-leucyl-tRNA(Leu) + L-phenylalanyl-tRNA(Phe) = cyclo(L-
CC phenylalanyl-L-leucyl) + H(+) + tRNA(Leu) + tRNA(Phe);
CC Xref=Rhea:RHEA:50940, Rhea:RHEA-COMP:9613, Rhea:RHEA-COMP:9622,
CC Rhea:RHEA-COMP:9668, Rhea:RHEA-COMP:9699, ChEBI:CHEBI:15378,
CC ChEBI:CHEBI:71608, ChEBI:CHEBI:78442, ChEBI:CHEBI:78494,
CC ChEBI:CHEBI:78531; EC=2.3.2.20;
CC Evidence={ECO:0000269|PubMed:19430487};
CC -!- SUBUNIT: Monomer. {ECO:0000269|PubMed:21296757}.
CC -!- MISCELLANEOUS: The reaction proceeds following a ping-pong mechanism
CC forming a covalent intermediate between an active site Ser-37 and the
CC L-phenylalanine residue. {ECO:0000305|PubMed:21296757}.
CC -!- SIMILARITY: Belongs to the CDPS family. {ECO:0000305}.
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DR EMBL; AY129235; AAN07909.1; -; Genomic_DNA.
DR PDB; 3OQV; X-ray; 1.90 A; A=2-239.
DR PDB; 4Q24; X-ray; 2.90 A; A=1-239.
DR PDBsum; 3OQV; -.
DR PDBsum; 4Q24; -.
DR AlphaFoldDB; Q8GED7; -.
DR SMR; Q8GED7; -.
DR KEGG; ag:AAN07909; -.
DR BRENDA; 2.3.2.20; 11755.
DR BRENDA; 2.3.2.22; 11755.
DR EvolutionaryTrace; Q8GED7; -.
DR GO; GO:0016755; F:aminoacyltransferase activity; IDA:UniProtKB.
DR GO; GO:0002780; P:antibacterial peptide 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; Transferase.
FT CHAIN 1..239
FT /note="Cyclo(L-leucyl-L-phenylalanyl) synthase"
FT /id="PRO_0000423355"
FT ACT_SITE 37
FT /note="Nucleophile"
FT /evidence="ECO:0000305|PubMed:21296757"
FT BINDING 40
FT /ligand="substrate"
FT /evidence="ECO:0000250"
FT BINDING 178..182
FT /ligand="substrate"
FT /evidence="ECO:0000250"
FT BINDING 202
FT /ligand="substrate"
FT /evidence="ECO:0000250"
FT SITE 40
FT /note="Could have a critical role in the catalytic
FT mechanism"
FT /evidence="ECO:0000250"
FT SITE 98
FT /note="Could be involved in aa-tRNA binding"
FT /evidence="ECO:0000250"
FT SITE 178
FT /note="Could be involved in aa-tRNA binding"
FT /evidence="ECO:0000250"
FT SITE 182
FT /note="Could have a critical role in the catalytic
FT mechanism"
FT /evidence="ECO:0000250"
FT SITE 200
FT /note="Essential for the cyclodipeptide synthase
FT specificity"
FT MUTAGEN 35
FT /note="G->A: Poorly active."
FT /evidence="ECO:0000269|PubMed:21296757"
FT MUTAGEN 37
FT /note="S->A: Inactive."
FT /evidence="ECO:0000269|PubMed:21296757"
FT MUTAGEN 37
FT /note="S->C: Does not completely abolish the enzymatic
FT activity."
FT /evidence="ECO:0000269|PubMed:21296757"
FT MUTAGEN 178
FT /note="Y->A: Almost inactive."
FT /evidence="ECO:0000269|PubMed:21296757"
FT MUTAGEN 178
FT /note="Y->F: Poorly active."
FT /evidence="ECO:0000269|PubMed:21296757"
FT MUTAGEN 182
FT /note="E->A: Inactive."
FT /evidence="ECO:0000269|PubMed:21296757"
FT MUTAGEN 182
FT /note="E->Q: Inactive."
FT /evidence="ECO:0000269|PubMed:21296757"
FT MUTAGEN 200
FT /note="L->N: It synthesizes mainly cyclo(L-Tyr-L-Leu) (cYL)
FT instead of cFL."
FT /evidence="ECO:0000269|PubMed:21296757"
FT MUTAGEN 202
FT /note="Y->F: It retains 11% of the enzymatic activity."
FT /evidence="ECO:0000269|PubMed:21296757"
FT STRAND 13..17
FT /evidence="ECO:0007829|PDB:4Q24"
FT HELIX 20..22
FT /evidence="ECO:0007829|PDB:4Q24"
FT HELIX 23..28
FT /evidence="ECO:0007829|PDB:4Q24"
FT STRAND 29..39
FT /evidence="ECO:0007829|PDB:3OQV"
FT HELIX 41..43
FT /evidence="ECO:0007829|PDB:4Q24"
FT HELIX 45..58
FT /evidence="ECO:0007829|PDB:3OQV"
FT STRAND 59..67
FT /evidence="ECO:0007829|PDB:3OQV"
FT HELIX 71..78
FT /evidence="ECO:0007829|PDB:3OQV"
FT HELIX 82..107
FT /evidence="ECO:0007829|PDB:3OQV"
FT HELIX 111..113
FT /evidence="ECO:0007829|PDB:3OQV"
FT STRAND 114..118
FT /evidence="ECO:0007829|PDB:3OQV"
FT HELIX 119..122
FT /evidence="ECO:0007829|PDB:3OQV"
FT HELIX 126..141
FT /evidence="ECO:0007829|PDB:3OQV"
FT HELIX 143..158
FT /evidence="ECO:0007829|PDB:3OQV"
FT STRAND 161..163
FT /evidence="ECO:0007829|PDB:3OQV"
FT HELIX 169..193
FT /evidence="ECO:0007829|PDB:3OQV"
FT STRAND 198..202
FT /evidence="ECO:0007829|PDB:3OQV"
FT HELIX 207..212
FT /evidence="ECO:0007829|PDB:3OQV"
FT STRAND 217..219
FT /evidence="ECO:0007829|PDB:4Q24"
FT STRAND 225..229
FT /evidence="ECO:0007829|PDB:3OQV"
FT HELIX 232..238
FT /evidence="ECO:0007829|PDB:3OQV"
SQ SEQUENCE 239 AA; 26774 MW; CD368019F6EF87F3 CRC64;
MLAGLVPAPD HGMREEILGD RSRLIRQRGE HALIGISAGN SYFSQKNTVM LLQWAGQRFE
RTDVVYVDTH IDEMLIADGR SAQEAERSVK RTLKDLRRRL RRSLESVGDH AERFRVRSLS
ELQETPEYRA VRERTDRAFE EDAEFATACE DMVRAVVMNR PGDGVGISAE HLRAGLNYVL
AEAPLFADSP GVFSVPSSVL CYHIDTPITA FLSRRETGFR AAEGQAYVVV RPQELADAA
