ID   BLAC_NOCFA              Reviewed;         313 AA.
AC   Q5YXD6; O30987;
DT   15-JAN-2008, integrated into UniProtKB/Swiss-Prot.
DT   15-JAN-2008, sequence version 2.
DT   27-MAR-2024, entry version 104.
DE   RecName: Full=Beta-lactamase FAR-1;
DE            EC=3.5.2.6;
DE   Flags: Precursor;
GN   Name=bla; Synonyms=far1; OrderedLocusNames=NFA_23080;
OS   Nocardia farcinica (strain IFM 10152).
OC   Bacteria; Actinomycetota; Actinomycetes; Mycobacteriales; Nocardiaceae;
OC   Nocardia.
OX   NCBI_TaxID=247156;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [GENOMIC DNA], ACTIVITY REGULATION, AND
RP   BIOPHYSICOCHEMICAL PROPERTIES.
RC   STRAIN=VIC;
RX   PubMed=10390216; DOI=10.1128/aac.43.7.1644;
RA   Laurent F., Poirel L., Naas T., Chaibi E.B., Labia R., Boiron P.,
RA   Nordmann P.;
RT   "Biochemical-genetic analysis and distribution of FAR-1, a class A beta-
RT   lactamase from Nocardia farcinica.";
RL   Antimicrob. Agents Chemother. 43:1644-1650(1999).
RN   [2]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC   STRAIN=IFM 10152;
RX   PubMed=15466710; DOI=10.1073/pnas.0406410101;
RA   Ishikawa J., Yamashita A., Mikami Y., Hoshino Y., Kurita H., Hotta K.,
RA   Shiba T., Hattori M.;
RT   "The complete genomic sequence of Nocardia farcinica IFM 10152.";
RL   Proc. Natl. Acad. Sci. U.S.A. 101:14925-14930(2004).
RN   [3]
RP   EVIDENCE OF MEMBRANE-BOUND LOCALIZATION.
RX   PubMed=8239595; DOI=10.1128/aac.37.9.1850;
RA   Steingrube V.A., Wallace R.J., Brown B.A., Zhang Y., Steele L.C., Young G.,
RA   Nash D.R.;
RT   "Partial characterization of Nocardia farcinica beta-lactamases.";
RL   Antimicrob. Agents Chemother. 37:1850-1855(1993).
CC   -!- FUNCTION: Confers high levels of resistance to amoxicillin,
CC       benzylpenicillin, piperacillin, ticarcillin and cephalothin. Also
CC       hydrolyzes aztreonam at a low level. Not active against ceftazidime,
CC       cefotaxime and imipenem.
CC   -!- CATALYTIC ACTIVITY:
CC       Reaction=a beta-lactam + H2O = a substituted beta-amino acid;
CC         Xref=Rhea:RHEA:20401, ChEBI:CHEBI:15377, ChEBI:CHEBI:35627,
CC         ChEBI:CHEBI:140347; EC=3.5.2.6; Evidence={ECO:0000255|PROSITE-
CC         ProRule:PRU10101};
CC   -!- ACTIVITY REGULATION: Inhibited by clavulanic acid, and at a low level
CC       by tazobactam and sulbactam. {ECO:0000269|PubMed:10390216}.
CC   -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC       Kinetic parameters:
CC         KM=30 uM for benzylpenicillin {ECO:0000269|PubMed:10390216};
CC         KM=50 uM for amoxicillin {ECO:0000269|PubMed:10390216};
CC         KM=31 uM for ticarcillin {ECO:0000269|PubMed:10390216};
CC         KM=45 uM for piperacillin {ECO:0000269|PubMed:10390216};
CC         KM=104 uM for cephalothin {ECO:0000269|PubMed:10390216};
CC         KM=400 uM for aztreonam {ECO:0000269|PubMed:10390216};
CC         Vmax=5.5 umol/sec/mg enzyme with benzylpenicillin as substrate
CC         {ECO:0000269|PubMed:10390216};
CC         Vmax=3.8 umol/sec/mg enzyme with amoxicillin as substrate
CC         {ECO:0000269|PubMed:10390216};
CC         Vmax=1.6 umol/sec/mg enzyme with ticarcillin as substrate
CC         {ECO:0000269|PubMed:10390216};
CC         Vmax=9.2 umol/sec/mg enzyme with piperacillin as substrate
CC         {ECO:0000269|PubMed:10390216};
CC         Vmax=0.13 umol/sec/mg enzyme with cephalothin as substrate
CC         {ECO:0000269|PubMed:10390216};
CC   -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000305}; Lipid-anchor
CC       {ECO:0000305}.
CC   -!- SIMILARITY: Belongs to the class-A beta-lactamase family.
CC       {ECO:0000305}.
CC   -!- SEQUENCE CAUTION:
CC       Sequence=AAB81957.1; Type=Frameshift; Evidence={ECO:0000305};
CC       Sequence=BAD57155.1; Type=Erroneous initiation; Evidence={ECO:0000305};
CC   ---------------------------------------------------------------------------
CC   Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms
CC   Distributed under the Creative Commons Attribution (CC BY 4.0) License
CC   ---------------------------------------------------------------------------
DR   EMBL; AF024601; AAB81957.1; ALT_FRAME; Genomic_DNA.
DR   EMBL; AP006618; BAD57155.1; ALT_INIT; Genomic_DNA.
DR   AlphaFoldDB; Q5YXD6; -.
DR   SMR; Q5YXD6; -.
DR   STRING; 247156.NFA_23080; -.
DR   KEGG; nfa:NFA_23080; -.
DR   eggNOG; COG2367; Bacteria.
DR   HOGENOM; CLU_031960_6_0_11; -.
DR   SABIO-RK; Q5YXD6; -.
DR   Proteomes; UP000006820; Chromosome.
DR   GO; GO:0005886; C:plasma membrane; IEA:UniProtKB-SubCell.
DR   GO; GO:0008800; F:beta-lactamase activity; IEA:UniProtKB-EC.
DR   GO; GO:0030655; P:beta-lactam antibiotic catabolic process; IEA:InterPro.
DR   GO; GO:0046677; P:response to antibiotic; IEA:UniProtKB-KW.
DR   Gene3D; 3.40.710.10; DD-peptidase/beta-lactamase superfamily; 1.
DR   InterPro; IPR012338; Beta-lactam/transpept-like.
DR   InterPro; IPR045155; Beta-lactam_cat.
DR   InterPro; IPR000871; Beta-lactam_class-A.
DR   InterPro; IPR023650; Beta-lactam_class-A_AS.
DR   PANTHER; PTHR35333; BETA-LACTAMASE; 1.
DR   PANTHER; PTHR35333:SF3; BETA-LACTAMASE2 DOMAIN-CONTAINING PROTEIN; 1.
DR   Pfam; PF13354; Beta-lactamase2; 1.
DR   PRINTS; PR00118; BLACTAMASEA.
DR   SUPFAM; SSF56601; beta-lactamase/transpeptidase-like; 1.
DR   PROSITE; PS00146; BETA_LACTAMASE_A; 1.
PE   1: Evidence at protein level;
KW   Antibiotic resistance; Cell membrane; Hydrolase; Lipoprotein; Membrane;
KW   Palmitate; Reference proteome; Signal.
FT   SIGNAL          1..28
FT                   /evidence="ECO:0000255"
FT   CHAIN           29..313
FT                   /note="Beta-lactamase FAR-1"
FT                   /id="PRO_0000313798"
FT   ACT_SITE        94
FT                   /note="Acyl-ester intermediate"
FT                   /evidence="ECO:0000250|UniProtKB:P9WKD3"
FT   ACT_SITE        190
FT                   /note="Proton acceptor"
FT                   /evidence="ECO:0000250|UniProtKB:P9WKD3"
FT   BINDING         154
FT                   /ligand="substrate"
FT                   /evidence="ECO:0000250|UniProtKB:P9WKD3"
FT   BINDING         258..260
FT                   /ligand="substrate"
FT                   /evidence="ECO:0000250"
FT   SITE            97
FT                   /note="Increases nucleophilicity of active site Ser"
FT                   /evidence="ECO:0000250|UniProtKB:P9WKD3"
FT   LIPID           29
FT                   /note="N-palmitoyl cysteine"
FT                   /evidence="ECO:0000255"
FT   LIPID           29
FT                   /note="S-diacylglycerol cysteine"
FT                   /evidence="ECO:0000255"
FT   CONFLICT        22
FT                   /note="V -> A (in Ref. 1; AAB81957)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        49
FT                   /note="A -> T (in Ref. 1; AAB81957)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        65
FT                   /note="F -> S (in Ref. 1; AAB81957)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        81
FT                   /note="V -> E (in Ref. 1; AAB81957)"
FT                   /evidence="ECO:0000305"
SQ   SEQUENCE   313 AA;  32566 MW;  EB60AB1DC46B841D CRC64;
     MPGVDISFLK KSGRRTMAAA AVIALLGGCG ADAGSEPATT AASTTAPSAA TDAATAEFAA
     LEQRFGARLG VYAVDTTSGA VVAYRADERF GMASTFKGLA CGALLREHPL SSGYFDQVVR
     YSREEVVSYS PVTETRVDTG MTVAELCHAT ITVSDNTAGN QILKLLGGPA GFTAFLRSLG
     DEVSRLDRWE TELNEVPPGE ERDTTTPAAV AANYRALVLG DVLAEPERAQ LRDWLVANTT
     GDQRIRAGVP AGWTVGDKTG GGSHGGNNDV AVAWTETGDP IVIALLSHRT DPAAKADNAL
     LAEATRAVVT ALR
//