THCL1_AMISM
ID THCL1_AMISM Reviewed; 14 AA.
AC P0C912;
DT 14-APR-2009, integrated into UniProtKB/Swiss-Prot.
DT 14-APR-2009, sequence version 1.
DT 17-JUN-2020, entry version 14.
DE RecName: Full=Amythiamicin A/B;
DE Contains:
DE RecName: Full=Amythiamicin C/D;
OS Amycolatopsis sp. (strain MI481-42F4 / FERM P-12739).
OC Bacteria; Actinobacteria; Pseudonocardiales; Pseudonocardiaceae;
OC Amycolatopsis; unclassified Amycolatopsis.
OX NCBI_TaxID=613028;
RN [1]
RP FUNCTION, SUBCELLULAR LOCATION, METHYLATION AT CYS-12, AND MASS
RP SPECTROMETRY.
RX PubMed=8040071; DOI=10.7164/antibiotics.47.668;
RA Shimanaka K., Kinoshita N., Iinuma H., Hamada M., Takeuchi T.;
RT "Novel antibiotics, amythiamicins. I. Taxonomy, fermentation, isolation,
RT physico-chemical properties, and antimicrobial activity.";
RL J. Antibiot. 47:668-674(1994).
RN [2]
RP SYNTHESIS.
RX PubMed=15069488; DOI=10.1039/b401580k;
RA Hughes R.A., Thompson S.P., Alcaraz L., Moody C.J.;
RT "Total synthesis of the thiopeptide amythiamicin D.";
RL Chem. Commun. (Camb.) 8:946-948(2004).
RN [3]
RP STRUCTURE BY NMR.
RX PubMed=7961165; DOI=10.7164/antibiotics.47.1145;
RA Shimanaka K., Takahashi Y., Iinuma H., Naganawa H., Takeuchi T.;
RT "Novel antibiotics, amythiamicins. II. Structure elucidation of
RT amythiamicin D.";
RL J. Antibiot. 47:1145-1152(1994).
RN [4]
RP STRUCTURE BY NMR, AND AMIDATION AT PRO-14.
RX PubMed=7961166; DOI=10.7164/antibiotics.47.1153;
RA Shimanaka K., Takahashi Y., Iinuma H., Naganawa H., Takeuchi T.;
RT "Novel antibiotics, amythiamicins. III. Structure elucidations of
RT amythiamicins A, B and C.";
RL J. Antibiot. 47:1153-1159(1994).
RN [5]
RP STRUCTURE BY NMR.
RX PubMed=17031436; DOI=10.1039/b609282a;
RA Lewis R.J., Hughes R.A., Alcaraz L., Thompson S.P., Moody C.J.;
RT "Solution structures of thiopeptide antibiotics.";
RL Chem. Commun. (Camb.) 40:4215-4217(2006).
CC -!- FUNCTION: Has bacteriocidal activity against Gram-positive bacteria
CC including multi-drug resistant strains such as S.aureus MS9610 and
CC methicillin-resistant S.aureus, but is not active against most Gram-
CC negative bacteria and fungi. {ECO:0000269|PubMed:8040071}.
CC -!- SUBCELLULAR LOCATION: Secreted {ECO:0000269|PubMed:8040071}.
CC -!- PTM: Maturation of thiazole and oxazole containing antibiotics involves
CC the enzymatic condensation of a Cys, Ser or Thr with the alpha-carbonyl
CC of the preceding amino acid to form a thioether or ether bond, then
CC dehydration to form a double bond with the alpha-amino nitrogen.
CC Thiazoline or oxazoline rings are dehydrogenated to form thiazole or
CC oxazole rings.
CC -!- PTM: Maturation of pyridinyl containing antibiotics involves the cross-
CC linking of a Ser and a Cys-Ser pair usually separated by 7 or 8
CC residues along the peptide chain. The Ser residues are dehydrated to
CC didehydroalanines, then bonded between their beta carbons. The alpha
CC carbonyl of the Cys condenses with the alpha carbon of the first Ser to
CC form a pyridinyl ring. The ring may be multiply dehydrogenated to form
CC a pyridine ring with loss of the amino nitrogen of the first Ser.
CC -!- PTM: The diketopiperazine ester in form C may be formed by cyclization
CC and transesterification of the C-terminal dipeptide.
CC -!- MASS SPECTROMETRY: [Amythiamicin A/B]: Mass=1182.2463; Method=FAB;
CC Note=Form A.; Evidence={ECO:0000269|PubMed:8040071};
CC -!- MASS SPECTROMETRY: [Amythiamicin A/B]: Mass=1200.2549; Method=FAB;
CC Note=Form B.; Evidence={ECO:0000269|PubMed:8040071};
CC -!- MASS SPECTROMETRY: [Amythiamicin C/D]: Mass=1183.2285; Method=FAB;
CC Note=Form C.; Evidence={ECO:0000269|PubMed:8040071};
CC -!- MASS SPECTROMETRY: [Amythiamicin C/D]: Mass=1031.1688; Method=FAB;
CC Note=Form D.; Evidence={ECO:0000269|PubMed:8040071};
CC -!- SIMILARITY: Belongs to the thiocillin family. {ECO:0000305}.
CC -!- CAUTION: It is possible that the 5-methylthiazole shown as derived from
CC Cys-4 may be instead derived from Thr. {ECO:0000305}.
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DR GO; GO:0005576; C:extracellular region; IEA:UniProtKB-SubCell.
DR GO; GO:0019835; P:cytolysis; IEA:UniProtKB-KW.
DR GO; GO:0042742; P:defense response to bacterium; IEA:UniProtKB-KW.
DR GO; GO:0008156; P:negative regulation of DNA replication; IEA:UniProtKB-KW.
PE 1: Evidence at protein level;
KW Amidation; Antibiotic; Antimicrobial; Bacteriocin;
KW DNA replication inhibitor; Methylation; Secreted; Thioether bond.
FT PEPTIDE 1..14
FT /note="Amythiamicin A/B"
FT /id="PRO_0000368029"
FT PEPTIDE 1..12
FT /note="Amythiamicin C/D"
FT /id="PRO_0000368030"
FT MOD_RES 3
FT /note="N4-methylasparagine"
FT /evidence="ECO:0000250|UniProtKB:Q7M0J8"
FT MOD_RES 12
FT /note="Cyclo[(prolylserin)-O-yl] cysteinate; in form C"
FT MOD_RES 12
FT /note="Cysteine methyl ester; in form D"
FT /evidence="ECO:0000269|PubMed:8040071"
FT MOD_RES 14
FT /note="Proline amide; in form A and form B"
FT /evidence="ECO:0000269|PubMed:7961166"
FT CROSSLNK 1..11
FT /note="Pyridine-2,5-dicarboxylic acid (Ser-Ser) (with C-
FT 10)"
FT CROSSLNK 1..10
FT /note="Pyridine-2,5-dicarboxylic acid (Ser-Cys) (with S-
FT 11)"
FT CROSSLNK 1..2
FT /note="Thiazole-4-carboxylic acid (Ser-Cys)"
FT CROSSLNK 3..4
FT /note="5-methylthiazole-4-carboxylic acid (Asn-Cys)"
FT CROSSLNK 5..6
FT /note="Thiazole-4-carboxylic acid (Val-Cys)"
FT CROSSLNK 8..9
FT /note="Thiazole-4-carboxylic acid (Val-Cys)"
FT CROSSLNK 9..10
FT /note="Thiazole-4-carboxylic acid (Cys-Cys)"
FT CROSSLNK 11..12
FT /note="Thiazole-4-carboxylic acid (Ser-Cys)"
FT CROSSLNK 12..13
FT /note="Oxazoline-4-carboxylic acid (Cys-Ser); in form A"
FT UNSURE 4
FT /note="C or T"
SQ SEQUENCE 14 AA; 1365 MW; 3EB862761A777DC8 CRC64;
SCNCVCGVCC SCSP
