ID BLAC_MYCTA Reviewed; 307 AA.
AC A5U493; P0A5I6; Q10670;
DT 11-SEP-2007, integrated into UniProtKB/Swiss-Prot.
DT 10-JUL-2007, sequence version 1.
DT 27-MAR-2024, entry version 87.
DE RecName: Full=Beta-lactamase {ECO:0000303|PubMed:9145897};
DE EC=3.5.2.6 {ECO:0000269|PubMed:9624479};
DE AltName: Full=Ambler class A beta-lactamase {ECO:0000303|PubMed:9145897};
DE Flags: Precursor;
GN Name=blaC; Synonyms=blaA {ECO:0000303|PubMed:9145897};
GN OrderedLocusNames=MRA_2082;
OS Mycobacterium tuberculosis (strain ATCC 25177 / H37Ra).
OC Bacteria; Actinomycetota; Actinomycetes; Mycobacteriales; Mycobacteriaceae;
OC Mycobacterium; Mycobacterium tuberculosis complex.
OX NCBI_TaxID=419947;
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RC STRAIN=ATCC 25177 / H37Ra;
RX PubMed=9145897; DOI=10.1128/aac.41.5.1182;
RA Hackbarth C.J., Unsal I., Chambers H.F.;
RT "Cloning and sequence analysis of a class A beta-lactamase from
RT Mycobacterium tuberculosis H37Ra.";
RL Antimicrob. Agents Chemother. 41:1182-1185(1997).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=ATCC 25177 / H37Ra;
RX PubMed=18584054; DOI=10.1371/journal.pone.0002375;
RA Zheng H., Lu L., Wang B., Pu S., Zhang X., Zhu G., Shi W., Zhang L.,
RA Wang H., Wang S., Zhao G., Zhang Y.;
RT "Genetic basis of virulence attenuation revealed by comparative genomic
RT analysis of Mycobacterium tuberculosis strain H37Ra versus H37Rv.";
RL PLoS ONE 3:E2375-E2375(2008).
RN [3]
RP FUNCTION, CATALYTIC ACTIVITY, BIOPHYSICOCHEMICAL PROPERTIES, ACTIVITY
RP REGULATION, AND SUBCELLULAR LOCATION.
RC STRAIN=ATCC 25177 / H37Ra;
RX PubMed=9624479; DOI=10.1128/aac.42.6.1375;
RA Voladri R.K., Lakey D.L., Hennigan S.H., Menzies B.E., Edwards K.M.,
RA Kernodle D.S.;
RT "Recombinant expression and characterization of the major beta-lactamase of
RT Mycobacterium tuberculosis.";
RL Antimicrob. Agents Chemother. 42:1375-1381(1998).
CC -!- FUNCTION: Extended spectrum beta-lactamase (ESBL) that inactivates
CC beta-lactam antibiotics by hydrolyzing the amide group of the beta-
CC lactam ring. Exhibits predominant penicillinase activity. Also displays
CC high levels of cephalosporinase activity as well as measurable activity
CC with carbapenems, including imipenem and meropenem. Plays a primary
CC role in the intrinsic resistance of M.tuberculosis to beta-lactam
CC antibiotics. {ECO:0000250|UniProtKB:P9WKD3,
CC ECO:0000269|PubMed:9624479}.
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;
CC Evidence={ECO:0000269|PubMed:9624479};
CC -!- ACTIVITY REGULATION: Is inhibited by clavulanate, sulbactam and m-
CC aminophenylboronate but not by EDTA. {ECO:0000269|PubMed:9624479}.
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=50 uM for benzylpenicillin (at pH 6.0)
CC {ECO:0000269|PubMed:9624479};
CC KM=38 uM for phenoxymethylpenicillin (at pH 6.0)
CC {ECO:0000269|PubMed:9624479};
CC KM=94 uM for amoxicillin (at pH 6.0) {ECO:0000269|PubMed:9624479};
CC KM=185 uM for azlocillin (at pH 6.0) {ECO:0000269|PubMed:9624479};
CC KM=81 uM for nitrocefin (at pH 6.0) {ECO:0000269|PubMed:9624479};
CC KM=798 uM for cephaloridine (at pH 6.0) {ECO:0000269|PubMed:9624479};
CC KM=490 uM for cefazolin (at pH 6.0) {ECO:0000269|PubMed:9624479};
CC KM=308 uM for cephalothin (at pH 6.0) {ECO:0000269|PubMed:9624479};
CC KM=680 uM for cephapirin (at pH 6.0) {ECO:0000269|PubMed:9624479};
CC KM=645 uM for cefamandole (at pH 6.0) {ECO:0000269|PubMed:9624479};
CC Note=kcat is 21 sec(-1) with benzylpenicillin as substrate. kcat is
CC 20 sec(-1) with phenoxymethylpenicillin as substrate. kcat is 2 sec(-
CC 1) with amoxicillin as substrate. kcat is 55 sec(-1) with azlocillin
CC as substrate. kcat is 31 sec(-1) with nitrocefin as substrate. kcat
CC is 8 sec(-1) with cephaloridine as substrate. kcat is 8 sec(-1) with
CC cefazolin as substrate. kcat is 8 sec(-1) with cephalothin as
CC substrate. kcat is 3 sec(-1) with cephapirin as substrate. kcat is 22
CC sec(-1) with cefamandole as substrate. Assays performed at pH 6.0.
CC {ECO:0000269|PubMed:9624479};
CC -!- SUBUNIT: Monomer. {ECO:0000250|UniProtKB:P9WKD3}.
CC -!- SUBCELLULAR LOCATION: Periplasm {ECO:0000250|UniProtKB:P9WKD3}.
CC Secreted {ECO:0000269|PubMed:9624479}.
CC -!- PTM: Exported by the Tat system. The position of the signal peptide
CC cleavage has not been experimentally proven.
CC {ECO:0000250|UniProtKB:P9WKD3}.
CC -!- SIMILARITY: Belongs to the class-A beta-lactamase family.
CC {ECO:0000305}.
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DR EMBL; U67924; AAB07556.1; -; Genomic_DNA.
DR EMBL; CP000611; ABQ73843.1; -; Genomic_DNA.
DR RefSeq; WP_003410677.1; NZ_CP016972.1.
DR AlphaFoldDB; A5U493; -.
DR SMR; A5U493; -.
DR GeneID; 45426045; -.
DR KEGG; mra:MRA_2082; -.
DR eggNOG; COG2367; Bacteria.
DR HOGENOM; CLU_031960_6_0_11; -.
DR SABIO-RK; A5U493; -.
DR EvolutionaryTrace; A5U493; -.
DR Proteomes; UP000001988; Chromosome.
DR GO; GO:0005576; C:extracellular region; IEA:UniProtKB-SubCell.
DR GO; GO:0042597; C:periplasmic space; 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; Hydrolase; Periplasm; Reference proteome; Secreted;
KW Signal.
FT SIGNAL 1..34
FT /note="Tat-type signal"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00648"
FT CHAIN 35..307
FT /note="Beta-lactamase"
FT /id="PRO_0000300061"
FT ACT_SITE 84
FT /note="Acyl-ester intermediate"
FT /evidence="ECO:0000250|UniProtKB:P9WKD3"
FT ACT_SITE 182
FT /note="Proton acceptor"
FT /evidence="ECO:0000250|UniProtKB:P9WKD3"
FT BINDING 142
FT /ligand="substrate"
FT /evidence="ECO:0000250|UniProtKB:P9WKD3"
FT BINDING 251..253
FT /ligand="substrate"
FT /evidence="ECO:0000250|UniProtKB:P9WKD3"
FT SITE 87
FT /note="Increases nucleophilicity of active site Ser"
FT /evidence="ECO:0000250|UniProtKB:P9WKD3"
FT SITE 117
FT /note="Functions as a gatekeeper residue that regulates
FT substrate accessibility to the enzyme active site"
FT /evidence="ECO:0000250|UniProtKB:P9WKD3"
SQ SEQUENCE 307 AA; 32568 MW; 448CB2A0E05F4315 CRC64;
MRNRGFGRRE LLVAMAMLVS VTGCARHASG ARPASTTLPA GADLADRFAE LERRYDARLG
VYVPATGTTA AIEYRADERF AFCSTFKAPL VAAVLHQNPL THLDKLITYT SDDIRSISPV
AQQHVQTGMT IGQLCDAAIR YSDGTAANLL LADLGGPGGG TAAFTGYLRS LGDTVSRLDA
EEPELNRDPP GDERDTTTPH AIALVLQQLV LGNALPPDKR ALLTDWMARN TTGAKRIRAG
FPADWKVIDK TGTGDYGRAN DIAVVWSPTG VPYVVAVMSD RAGGGYDAEP REALLAEAAT
CVAGVLA
//
