ID   STTH_STRA9              Reviewed;         276 AA.
AC   Q1MW86;
DT   05-SEP-2012, integrated into UniProtKB/Swiss-Prot.
DT   05-SEP-2012, sequence version 2.
DT   03-AUG-2022, entry version 46.
DE   RecName: Full=Streptothricin hydrolase;
DE            EC=3.5.2.19;
GN   Name=sttH;
OS   Streptomyces albulus.
OC   Bacteria; Actinobacteria; Streptomycetales; Streptomycetaceae;
OC   Streptomyces.
OX   NCBI_TaxID=68570;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [GENOMIC DNA], FUNCTION, CATALYTIC ACTIVITY, COFACTOR,
RP   AND SUBUNIT.
RC   STRAIN=JCM 5054 / NBRC 14147 / KCC S-1054;
RX   PubMed=16641084; DOI=10.1074/jbc.m602294200;
RA   Hamano Y., Matsuura N., Kitamura M., Takagi H.;
RT   "A novel enzyme conferring streptothricin resistance alters the toxicity of
RT   streptothricin D from broad-spectrum to bacteria-specific.";
RL   J. Biol. Chem. 281:16842-16848(2006).
RN   [2]
RP   IDENTIFICATION OF START SITE, FUNCTION, CATALYTIC ACTIVITY,
RP   BIOPHYSICOCHEMICAL PROPERTIES, AND MUTAGENESIS OF CYS-176.
RC   STRAIN=JCM 5054 / NBRC 14147 / KCC S-1054;
RX   PubMed=19897889; DOI=10.1271/bbb.90499;
RA   Maruyama C., Hamano Y.;
RT   "The biological function of the bacterial isochorismatase-like hydrolase
RT   SttH.";
RL   Biosci. Biotechnol. Biochem. 73:2494-2500(2009).
CC   -!- FUNCTION: Catalyzes the hydrolysis of the amide bond of streptolidine
CC       lactam, thereby conferring streptothricin (ST) resistance. Can
CC       hydrolyze streptothricin-F and streptothricin-D. However, this strain
CC       is believed to be a ST nonproducer, which raises the possibility that
CC       its true role may not be its involvement in self-resistance to STs. May
CC       catalyze the hydrolysis of naturally occurring cyclic amide compounds
CC       that are structurally related to STs. {ECO:0000269|PubMed:16641084,
CC       ECO:0000269|PubMed:19897889}.
CC   -!- CATALYTIC ACTIVITY:
CC       Reaction=H2O + streptothricin F = streptothricin F acid;
CC         Xref=Rhea:RHEA:28138, ChEBI:CHEBI:15377, ChEBI:CHEBI:60822,
CC         ChEBI:CHEBI:60838; EC=3.5.2.19;
CC         Evidence={ECO:0000269|PubMed:16641084, ECO:0000269|PubMed:19897889};
CC   -!- COFACTOR:
CC       Note=Does not require a metal cofactor. {ECO:0000269|PubMed:16641084};
CC   -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC       Kinetic parameters:
CC         KM=3.1 mM for streptothricin-F {ECO:0000269|PubMed:19897889};
CC         KM=17.2 mM for streptothricin-D {ECO:0000269|PubMed:19897889};
CC         Vmax=48.3 umol/min/mg enzyme with streptothricin-F as substrate
CC         {ECO:0000269|PubMed:19897889};
CC         Vmax=199.7 umol/min/mg enzyme with streptothricin-D as substrate
CC         {ECO:0000269|PubMed:19897889};
CC       pH dependence:
CC         Optimum pH is 6.5. {ECO:0000269|PubMed:19897889};
CC       Temperature dependence:
CC         Optimum temperature is 45 degrees Celsius.
CC         {ECO:0000269|PubMed:19897889};
CC   -!- SUBUNIT: Homodimer. {ECO:0000269|PubMed:16641084}.
CC   -!- SIMILARITY: Belongs to the isochorismatase family. {ECO:0000305}.
CC   -!- SEQUENCE CAUTION:
CC       Sequence=BAE93577.1; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={ECO:0000305};
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DR   EMBL; AB248874; BAE93577.1; ALT_INIT; Genomic_DNA.
DR   AlphaFoldDB; Q1MW86; -.
DR   SMR; Q1MW86; -.
DR   KEGG; ag:BAE93577; -.
DR   BioCyc; MetaCyc:MON-15931; -.
DR   BRENDA; 3.5.2.19; 7858.
DR   GO; GO:0016812; F:hydrolase activity, acting on carbon-nitrogen (but not peptide) bonds, in cyclic amides; IDA:UniProtKB.
DR   GO; GO:0046677; P:response to antibiotic; IEA:UniProtKB-KW.
DR   Gene3D; 3.40.50.850; -; 1.
DR   InterPro; IPR000868; Isochorismatase-like.
DR   InterPro; IPR036380; Isochorismatase-like_sf.
DR   Pfam; PF00857; Isochorismatase; 1.
DR   SUPFAM; SSF52499; SSF52499; 1.
PE   1: Evidence at protein level;
KW   Antibiotic resistance; Hydrolase.
FT   CHAIN           1..276
FT                   /note="Streptothricin hydrolase"
FT                   /id="PRO_0000418975"
FT   REGION          250..276
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   ACT_SITE        176
FT                   /note="Nucleophile"
FT                   /evidence="ECO:0000305"
FT   MUTAGEN         176
FT                   /note="C->S: Loss of activity."
FT                   /evidence="ECO:0000269|PubMed:19897889"
SQ   SEQUENCE   276 AA;  28255 MW;  005A61B88C7B28FC CRC64;
     MIRPDRCPWQ PCPSGRYLSR PSGRVPRSTM MTPMTAMPAV TAMPPETAAP PETAAPARPL
     RPVQALLVVD VQTAFVSGAE AVPEAARVLD RTRGLLARAR TAGALVVHLQ NDGAPGAVDA
     PHTPGWELHL PVEPGPREHV VRKTEDDGFA DTGLGALLDA AGVTELAVCG VLSEMCVAAT
     ARTALELGHR VVLPHDAHAT YDIPAAPDIS DTVPAAMSSR AAEWALGDEV EIVPRAAAVP
     FVAPPLAPAP EAPAAAAAPA AGTGLSPAGP PPAPAR