BLAC_MYCTU
ID BLAC_MYCTU Reviewed; 307 AA.
AC P9WKD3; L0T8I9; P0A5I6; P0C5C1; Q10670;
DT 16-APR-2014, integrated into UniProtKB/Swiss-Prot.
DT 16-APR-2014, sequence version 1.
DT 03-AUG-2022, entry version 44.
DE RecName: Full=Beta-lactamase {ECO:0000303|PubMed:15699201};
DE EC=3.5.2.6 {ECO:0000269|PubMed:16870770, ECO:0000269|PubMed:17915954, ECO:0000269|PubMed:19251630, ECO:0000269|PubMed:20353175};
DE AltName: Full=Ambler class A beta-lactamase {ECO:0000303|PubMed:17915954};
DE Flags: Precursor;
GN Name=blaC {ECO:0000303|PubMed:15699201}; Synonyms=blaA;
GN OrderedLocusNames=Rv2068c; ORFNames=MTCY49.07c;
OS Mycobacterium tuberculosis (strain ATCC 25618 / H37Rv).
OC Bacteria; Actinobacteria; Corynebacteriales; Mycobacteriaceae;
OC Mycobacterium; Mycobacterium tuberculosis complex.
OX NCBI_TaxID=83332;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=ATCC 25618 / H37Rv;
RX PubMed=9634230; DOI=10.1038/31159;
RA Cole S.T., Brosch R., Parkhill J., Garnier T., Churcher C.M., Harris D.E.,
RA Gordon S.V., Eiglmeier K., Gas S., Barry C.E. III, Tekaia F., Badcock K.,
RA Basham D., Brown D., Chillingworth T., Connor R., Davies R.M., Devlin K.,
RA Feltwell T., Gentles S., Hamlin N., Holroyd S., Hornsby T., Jagels K.,
RA Krogh A., McLean J., Moule S., Murphy L.D., Oliver S., Osborne J.,
RA Quail M.A., Rajandream M.A., Rogers J., Rutter S., Seeger K., Skelton S.,
RA Squares S., Squares R., Sulston J.E., Taylor K., Whitehead S.,
RA Barrell B.G.;
RT "Deciphering the biology of Mycobacterium tuberculosis from the complete
RT genome sequence.";
RL Nature 393:537-544(1998).
RN [2]
RP EXPORT VIA THE TAT-SYSTEM, MUTAGENESIS OF 8-ARG-ARG-9, AND SUBCELLULAR
RP LOCATION.
RC STRAIN=ATCC 25618 / H37Rv;
RX PubMed=16267291; DOI=10.1128/jb.187.22.7667-7679.2005;
RA McDonough J.A., Hacker K.E., Flores A.R., Pavelka M.S. Jr., Braunstein M.;
RT "The twin-arginine translocation pathway of Mycobacterium smegmatis is
RT functional and required for the export of mycobacterial beta-lactamases.";
RL J. Bacteriol. 187:7667-7679(2005).
RN [3]
RP DISRUPTION PHENOTYPE.
RC STRAIN=ATCC 25618 / H37Rv;
RX PubMed=15699201; DOI=10.1099/mic.0.27629-0;
RA Flores A.R., Parsons L.M., Pavelka M.S. Jr.;
RT "Genetic analysis of the beta-lactamases of Mycobacterium tuberculosis and
RT Mycobacterium smegmatis and susceptibility to beta-lactam antibiotics.";
RL Microbiology 151:521-532(2005).
RN [4]
RP FUNCTION, CATALYTIC ACTIVITY, ACTIVITY REGULATION, SUBUNIT,
RP BIOPHYSICOCHEMICAL PROPERTIES, AND SUBSTRATE SPECIFICITY.
RX PubMed=17915954; DOI=10.1021/bi701506h;
RA Hugonnet J.E., Blanchard J.S.;
RT "Irreversible inhibition of the Mycobacterium tuberculosis beta-lactamase
RT by clavulanate.";
RL Biochemistry 46:11998-12004(2007).
RN [5]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC STRAIN=ATCC 25618 / H37Rv;
RX PubMed=21969609; DOI=10.1074/mcp.m111.011627;
RA Kelkar D.S., Kumar D., Kumar P., Balakrishnan L., Muthusamy B., Yadav A.K.,
RA Shrivastava P., Marimuthu A., Anand S., Sundaram H., Kingsbury R.,
RA Harsha H.C., Nair B., Prasad T.S., Chauhan D.S., Katoch K., Katoch V.M.,
RA Kumar P., Chaerkady R., Ramachandran S., Dash D., Pandey A.;
RT "Proteogenomic analysis of Mycobacterium tuberculosis by high resolution
RT mass spectrometry.";
RL Mol. Cell. Proteomics 10:M111.011627-M111.011627(2011).
RN [6]
RP BIOTECHNOLOGY.
RX PubMed=23000993; DOI=10.1038/nchem.1435;
RA Xie H., Mire J., Kong Y., Chang M., Hassounah H.A., Thornton C.N.,
RA Sacchettini J.C., Cirillo J.D., Rao J.;
RT "Rapid point-of-care detection of the tuberculosis pathogen using a BlaC-
RT specific fluorogenic probe.";
RL Nat. Chem. 4:802-809(2012).
RN [7]
RP BIOTECHNOLOGY.
RX PubMed=24989449; DOI=10.1002/anie.201405243;
RA Cheng Y., Xie H., Sule P., Hassounah H., Graviss E.A., Kong Y.,
RA Cirillo J.D., Rao J.;
RT "Fluorogenic probes with substitutions at the 2 and 7 positions of
RT cephalosporin are highly BlaC-specific for rapid Mycobacterium tuberculosis
RT detection.";
RL Angew. Chem. Int. Ed. Engl. 53:9360-9364(2014).
RN [8]
RP X-RAY CRYSTALLOGRAPHY (1.72 ANGSTROMS) OF 41-307, FUNCTION, CATALYTIC
RP ACTIVITY, SUBSTRATE SPECIFICITY, AND BIOPHYSICOCHEMICAL PROPERTIES.
RC STRAIN=ATCC 25618 / H37Rv;
RX PubMed=16870770; DOI=10.1128/aac.00320-06;
RA Wang F., Cassidy C., Sacchettini J.C.;
RT "Crystal structure and activity studies of the Mycobacterium tuberculosis
RT beta-lactamase reveal its critical role in resistance to beta-lactam
RT antibiotics.";
RL Antimicrob. Agents Chemother. 50:2762-2771(2006).
RN [9]
RP X-RAY CRYSTALLOGRAPHY (1.70 ANGSTROMS) OF 43-307 IN COVALENT COMPLEX WITH
RP CLAVULANATE INHIBITOR, AND ACTIVITY REGULATION.
RC STRAIN=ATCC 25618 / H37Rv;
RX PubMed=18422342; DOI=10.1021/bi8001055;
RA Tremblay L.W., Hugonnet J.E., Blanchard J.S.;
RT "Structure of the covalent adduct formed between Mycobacterium tuberculosis
RT beta-lactamase and clavulanate.";
RL Biochemistry 47:5312-5316(2008).
RN [10]
RP X-RAY CRYSTALLOGRAPHY (1.80 ANGSTROMS) OF 43-307 IN COVALENT COMPLEX WITH
RP MEROPENEM, FUNCTION, CATALYTIC ACTIVITY, ACTIVITY REGULATION, AND
RP BIOPHYSICOCHEMICAL PROPERTIES.
RX PubMed=19251630; DOI=10.1126/science.1167498;
RA Hugonnet J.E., Tremblay L.W., Boshoff H.I., Barry C.E., Blanchard J.S.;
RT "Meropenem-clavulanate is effective against extensively drug-resistant
RT Mycobacterium tuberculosis.";
RL Science 323:1215-1218(2009).
RN [11]
RP X-RAY CRYSTALLOGRAPHY (1.30 ANGSTROMS) OF 43-307 IN COVALENT COMPLEXES WITH
RP CARBAPENEMS, FUNCTION, CATALYTIC ACTIVITY, BIOPHYSICOCHEMICAL PROPERTIES,
RP ACTIVE SITE, AND REACTION MECHANISM.
RX PubMed=20353175; DOI=10.1021/bi100232q;
RA Tremblay L.W., Fan F., Blanchard J.S.;
RT "Biochemical and structural characterization of Mycobacterium tuberculosis
RT beta-lactamase with the carbapenems ertapenem and doripenem.";
RL Biochemistry 49:3766-3773(2010).
RN [12]
RP X-RAY CRYSTALLOGRAPHY (1.22 ANGSTROMS) OF 43-307 OF MUTANTS ALA-87 AND
RP ALA-182 IN MICHAELIS COMPLEX AND COVALENT COMPLEX WITH CEFAMANDOLE, ACTIVE
RP SITE, REACTION MECHANISM, AND MUTAGENESIS OF LYS-87 AND GLU-182.
RX PubMed=20961112; DOI=10.1021/bi1015088;
RA Tremblay L.W., Xu H., Blanchard J.S.;
RT "Structures of the Michaelis complex (1.2 A) and the covalent acyl
RT intermediate (2.0 A) of cefamandole bound in the active sites of the
RT Mycobacterium tuberculosis beta-lactamase K73A and E166A mutants.";
RL Biochemistry 49:9685-9687(2010).
RN [13]
RP X-RAY CRYSTALLOGRAPHY (2.29 ANGSTROMS) OF 43-307 IN COVALENT COMPLEX WITH
RP NXL104 INHIBITOR, AND ACTIVITY REGULATION.
RX PubMed=22587688; DOI=10.1021/bi300508r;
RA Xu H., Hazra S., Blanchard J.S.;
RT "NXL104 irreversibly inhibits the beta-lactamase from Mycobacterium
RT tuberculosis.";
RL Biochemistry 51:4551-4557(2012).
RN [14]
RP X-RAY CRYSTALLOGRAPHY (2.10 ANGSTROMS) OF 43-307 OF MUTANT ALA-236,
RP ACTIVITY REGULATION, AND MUTAGENESIS OF SER-142; ARG-236 AND THR-253.
RX PubMed=24060876; DOI=10.1128/aac.01253-13;
RA Kurz S.G., Wolff K.A., Hazra S., Bethel C.R., Hujer A.M., Smith K.M.,
RA Xu Y., Tremblay L.W., Blanchard J.S., Nguyen L., Bonomo R.A.;
RT "Can inhibitor-resistant substitutions in the Mycobacterium tuberculosis
RT beta-Lactamase BlaC lead to clavulanate resistance?: a biochemical
RT rationale for the use of beta-lactam-beta-lactamase inhibitor
RT combinations.";
RL Antimicrob. Agents Chemother. 57:6085-6096(2013).
RN [15]
RP X-RAY CRYSTALLOGRAPHY (2.85 ANGSTROMS) OF 32-307, AND MUTAGENESIS OF
RP ILE-117.
RX PubMed=24023821; DOI=10.1371/journal.pone.0073123;
RA Feiler C., Fisher A.C., Boock J.T., Marrichi M.J., Wright L.,
RA Schmidpeter P.A., Blankenfeldt W., Pavelka M., DeLisa M.P.;
RT "Directed evolution of Mycobacterium tuberculosis beta-lactamase reveals
RT gatekeeper residue that regulates antibiotic resistance and catalytic
RT efficiency.";
RL PLoS ONE 8:E73123-E73123(2013).
CC -!- FUNCTION: Extended spectrum beta-lactamase (ESBL) that inactivates
CC beta-lactam antibiotics by hydrolyzing the amide group of the beta-
CC lactam ring. Displays high levels of penicillinase and cephalosporinase
CC activity as well as measurable activity with carbapenems, including
CC imipenem and meropenem. Plays a primary role in the intrinsic
CC resistance of M.tuberculosis to beta-lactam antibiotics.
CC {ECO:0000269|PubMed:15699201, ECO:0000269|PubMed:16870770,
CC ECO:0000269|PubMed:17915954, ECO:0000269|PubMed:19251630,
CC ECO:0000269|PubMed:20353175}.
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:16870770, ECO:0000269|PubMed:17915954,
CC ECO:0000269|PubMed:19251630, ECO:0000269|PubMed:20353175};
CC -!- ACTIVITY REGULATION: Is inhibited by sulbactam, tazobactam, and
CC clavulanate. Sulbactam inhibits the enzyme competitively and reversibly
CC with respect to nitrocefin. Tazobactam inhibits the enzyme in a time-
CC dependent manner, but the activity of the enzyme reappears due to the
CC slow hydrolysis of the covalently acylated enzyme. In contrast,
CC clavulanate reacts with the enzyme quickly to form hydrolytically
CC stable, inactive forms of the enzyme, via irreversible acylation of the
CC catalytic serine residue. Clavulanate has potential to be used in
CC combination with approved beta-lactam antibiotics to treat multi-drug
CC resistant (MDR) and extremely drug resistant (XDR) strains of
CC M.tuberculosis. Is also irreversibly inhibited by NXL104, which forms
CC an extremely stable carbamoyl adduct with the enzyme but shows an
CC inhibition efficiency more than 100-fold lower than that of
CC clavulanate. Is inhibited by carbapenems, that are very poor substrates
CC for the enzyme. {ECO:0000269|PubMed:17915954,
CC ECO:0000269|PubMed:18422342, ECO:0000269|PubMed:19251630,
CC ECO:0000269|PubMed:22587688, ECO:0000269|PubMed:24060876}.
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=8 uM for ampicillin (at pH 6.4) {ECO:0000269|PubMed:17915954};
CC KM=22 uM for amoxicillin (at pH 6.4) {ECO:0000269|PubMed:17915954};
CC KM=19 uM for penicillin G (at pH 6.4) {ECO:0000269|PubMed:17915954};
CC KM=69 uM for penicillin V (at pH 6.4) {ECO:0000269|PubMed:17915954};
CC KM=59 uM for piperacillin (at pH 6.4) {ECO:0000269|PubMed:17915954};
CC KM=114 uM for cephalosporin C (at pH 6.4)
CC {ECO:0000269|PubMed:17915954};
CC KM=152 uM for cephalotin (at pH 6.4) {ECO:0000269|PubMed:17915954};
CC KM=5100 uM for cefuroxime (at pH 6.4) {ECO:0000269|PubMed:17915954};
CC KM=184 uM for cefamandole (at pH 6.4) {ECO:0000269|PubMed:17915954};
CC KM=127 uM for cefoxitin (at pH 6.4) {ECO:0000269|PubMed:17915954};
CC KM=280 uM for ceftazidime (at pH 6.4) {ECO:0000269|PubMed:17915954};
CC KM=520 uM for ceftriaxone (at pH 6.4) {ECO:0000269|PubMed:17915954};
CC KM=5570 uM for cefotaxime (at pH 6.4) {ECO:0000269|PubMed:17915954};
CC KM=57 uM for nitrocefin (at pH 6.4) {ECO:0000269|PubMed:17915954};
CC KM=195 uM for CENTA (at pH 6.4) {ECO:0000269|PubMed:17915954};
CC KM=9.4 uM for imipenem (at pH 6.4) {ECO:0000269|PubMed:17915954};
CC KM=3.4 uM for meropenem (at pH 6.4) {ECO:0000269|PubMed:17915954};
CC KM=63 uM for ampicillin (at pH 7.5) {ECO:0000269|PubMed:16870770};
CC KM=117 uM for cephalotin (at pH 7.5) {ECO:0000269|PubMed:16870770};
CC KM=195 uM for cefoxitin (at pH 7.5) {ECO:0000269|PubMed:16870770};
CC KM=593 uM for ceftazidime (at pH 7.5) {ECO:0000269|PubMed:16870770};
CC KM=279 uM for meropenem (at pH 7.5) {ECO:0000269|PubMed:16870770};
CC KM=3.4 uM for meropenem (at pH 6.5) {ECO:0000269|PubMed:19251630};
CC KM=0.18 uM for doripenem (at pH 6.5) {ECO:0000269|PubMed:20353175};
CC KM=0.18 uM for ertapenem (at pH 6.5) {ECO:0000269|PubMed:20353175};
CC KM=55 uM for faropenem (at pH 6.5) {ECO:0000269|PubMed:20353175};
CC Note=kcat is 600 min(-1) with ampicillin as substrate. kcat is 340
CC min(-1) with amoxicillin as substrate. kcat is 560 min(-1) with
CC penicillin G as substrate. kcat is 2100 min(-1) with penicillin V as
CC substrate. kcat is 690 min(-1) with piperacillin as substrate. kcat
CC is 1070 min(-1) with cephalosporin C as substrate. kcat is 490 min(-
CC 1) with cephalotin as substrate. kcat is 490 min(-1) with cefuroxime
CC as substrate. kcat is 3500 min(-1) with cefamandole as substrate.
CC kcat is 48 min(-1) with cefoxitin as substrate. kcat is 2.0 min(-1)
CC with ceftazidime as substrate. kcat is 49 min(-1) with ceftriaxone as
CC substrate. kcat is 380 min(-1) with cefotaxime as substrate. kcat is
CC 6680 min(-1) with nitrocefin as substrate. kcat is 1770 min(-1) with
CC CENTA as substrate. kcat is 10 min(-1) with imipenem as substrate.
CC kcat is 0.08 min(-1) with meropenem as substrate. Assays above
CC performed at pH 6.4. kcat is 18.5 sec(-1) with ampicillin as
CC substrate. kcat is 12.1 sec(-1) with cephalotin as substrate. kcat is
CC 1.1 sec(-1) with cefoxitin as substrate. kcat is 0.2 sec(-1) with
CC ceftazidime as substrate. kcat is 0.9 sec(-1) with meropenem as
CC substrate. Assays above performed at pH 7.5. kcat is 0.08 min(-1)
CC with meropenem as substrate at pH 6.5. kcat is 0.016 min(-1) with
CC doripenem as substrate. kcat is 0.017 min(-1) with ertapenem as
CC substrate. kcat is 0.65 min(-1) with faropenem as substrate. Assays
CC above performed at pH 6.5. {ECO:0000269|PubMed:16870770,
CC ECO:0000269|PubMed:17915954, ECO:0000269|PubMed:19251630,
CC ECO:0000269|PubMed:20353175};
CC -!- SUBUNIT: Monomer. {ECO:0000269|PubMed:17915954}.
CC -!- SUBCELLULAR LOCATION: Cell inner membrane
CC {ECO:0000303|PubMed:15699201}. Periplasm {ECO:0000305|PubMed:16267291}.
CC Secreted {ECO:0000250|UniProtKB:A5U493}.
CC -!- INDUCTION: Constitutively expressed. {ECO:0000303|PubMed:24023821}.
CC -!- PTM: Exported by the Tat system. The position of the signal peptide
CC cleavage has not been experimentally proven.
CC {ECO:0000269|PubMed:16267291}.
CC -!- DISRUPTION PHENOTYPE: Cells lacking this gene become significantly more
CC susceptible (16- to 32-fold) to penicillins as well as third-generation
CC cephalosporins and carbapenems. They have no detectable beta-lactamase
CC activity. {ECO:0000269|PubMed:15699201}.
CC -!- BIOTECHNOLOGY: Can be used as a biomarker, which together with BlaC-
CC specific fluorogenic substrates, allows a rapid and accurate detection
CC of very low numbers of M.tuberculosis for the clinical diagnosis of
CC tuberculosis in sputum and other specimens.
CC {ECO:0000269|PubMed:23000993, ECO:0000269|PubMed:24989449}.
CC -!- SIMILARITY: Belongs to the class-A beta-lactamase family.
CC {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; AL123456; CCP44842.1; -; Genomic_DNA.
DR PIR; G70764; G70764.
DR RefSeq; NP_216584.1; NC_000962.3.
DR RefSeq; WP_003410677.1; NZ_NVQJ01000047.1.
DR PDB; 2GDN; X-ray; 1.72 A; A=41-307.
DR PDB; 3CG5; X-ray; 1.70 A; A=43-307.
DR PDB; 3DWZ; X-ray; 1.80 A; A=43-307.
DR PDB; 3IQA; X-ray; 2.20 A; A=43-307.
DR PDB; 3M6B; X-ray; 1.30 A; A=43-307.
DR PDB; 3M6H; X-ray; 1.99 A; A=43-307.
DR PDB; 3N6I; X-ray; 2.00 A; A=43-307.
DR PDB; 3N7W; X-ray; 1.70 A; A=43-307.
DR PDB; 3N8L; X-ray; 1.40 A; A=43-307.
DR PDB; 3N8R; X-ray; 1.41 A; A=43-307.
DR PDB; 3N8S; X-ray; 2.00 A; A=43-307.
DR PDB; 3NBL; X-ray; 2.00 A; A=43-307.
DR PDB; 3NC8; X-ray; 1.50 A; A=43-307.
DR PDB; 3NCK; X-ray; 2.80 A; A=43-307.
DR PDB; 3NDE; X-ray; 1.70 A; A=43-307.
DR PDB; 3NDG; X-ray; 1.90 A; A=43-307.
DR PDB; 3NY4; X-ray; 1.22 A; A=43-307.
DR PDB; 3VFF; X-ray; 2.78 A; A/B/C/D=43-307.
DR PDB; 3VFH; X-ray; 2.57 A; A/B/C/D=43-307.
DR PDB; 3ZHH; X-ray; 2.85 A; A/B/C/D=32-307.
DR PDB; 4DF6; X-ray; 2.29 A; A=43-307.
DR PDB; 4EBL; X-ray; 2.10 A; A/B/C/D=43-307.
DR PDB; 4EBN; X-ray; 2.85 A; A/B/C/D=43-307.
DR PDB; 4EBP; X-ray; 2.29 A; A/B/C/D=43-307.
DR PDB; 4JLF; X-ray; 2.10 A; A=43-307.
DR PDB; 4Q8I; X-ray; 1.90 A; A=41-307.
DR PDB; 4QB8; X-ray; 1.76 A; A=42-307.
DR PDB; 4QHC; X-ray; 1.90 A; A=42-307.
DR PDB; 4X6T; X-ray; 1.40 A; A=45-307.
DR PDB; 5NJ2; X-ray; 1.19 A; A/B=43-307.
DR PDB; 5OYO; X-ray; 2.10 A; A/B=43-307.
DR PDB; 6B5X; X-ray; 2.45 A; A/B/C/D=41-307.
DR PDB; 6B5Y; X-ray; 2.75 A; A/B/C/D=41-307.
DR PDB; 6B68; X-ray; 2.15 A; A/B/C/D=41-307.
DR PDB; 6B69; X-ray; 2.20 A; A/B/C/D=41-307.
DR PDB; 6B6A; X-ray; 2.30 A; A/B/C/D=41-307.
DR PDB; 6B6B; X-ray; 1.80 A; A=41-307.
DR PDB; 6B6C; X-ray; 1.90 A; A=41-307.
DR PDB; 6B6D; X-ray; 1.80 A; A=41-307.
DR PDB; 6B6E; X-ray; 1.90 A; A=41-307.
DR PDB; 6B6F; X-ray; 2.05 A; A=41-307.
DR PDB; 6N14; X-ray; 1.52 A; A=39-307.
DR PDB; 7A5T; X-ray; 1.40 A; A=43-307.
DR PDB; 7A5U; X-ray; 1.50 A; A=43-307.
DR PDB; 7A5W; X-ray; 1.40 A; A=43-307.
DR PDB; 7A71; X-ray; 1.40 A; A=43-307.
DR PDB; 7A72; X-ray; 1.30 A; A=43-307.
DR PDB; 7A74; X-ray; 1.60 A; A=41-307.
DR PDBsum; 2GDN; -.
DR PDBsum; 3CG5; -.
DR PDBsum; 3DWZ; -.
DR PDBsum; 3IQA; -.
DR PDBsum; 3M6B; -.
DR PDBsum; 3M6H; -.
DR PDBsum; 3N6I; -.
DR PDBsum; 3N7W; -.
DR PDBsum; 3N8L; -.
DR PDBsum; 3N8R; -.
DR PDBsum; 3N8S; -.
DR PDBsum; 3NBL; -.
DR PDBsum; 3NC8; -.
DR PDBsum; 3NCK; -.
DR PDBsum; 3NDE; -.
DR PDBsum; 3NDG; -.
DR PDBsum; 3NY4; -.
DR PDBsum; 3VFF; -.
DR PDBsum; 3VFH; -.
DR PDBsum; 3ZHH; -.
DR PDBsum; 4DF6; -.
DR PDBsum; 4EBL; -.
DR PDBsum; 4EBN; -.
DR PDBsum; 4EBP; -.
DR PDBsum; 4JLF; -.
DR PDBsum; 4Q8I; -.
DR PDBsum; 4QB8; -.
DR PDBsum; 4QHC; -.
DR PDBsum; 4X6T; -.
DR PDBsum; 5NJ2; -.
DR PDBsum; 5OYO; -.
DR PDBsum; 6B5X; -.
DR PDBsum; 6B5Y; -.
DR PDBsum; 6B68; -.
DR PDBsum; 6B69; -.
DR PDBsum; 6B6A; -.
DR PDBsum; 6B6B; -.
DR PDBsum; 6B6C; -.
DR PDBsum; 6B6D; -.
DR PDBsum; 6B6E; -.
DR PDBsum; 6B6F; -.
DR PDBsum; 6N14; -.
DR PDBsum; 7A5T; -.
DR PDBsum; 7A5U; -.
DR PDBsum; 7A5W; -.
DR PDBsum; 7A71; -.
DR PDBsum; 7A72; -.
DR PDBsum; 7A74; -.
DR AlphaFoldDB; P9WKD3; -.
DR SMR; P9WKD3; -.
DR STRING; 83332.Rv2068c; -.
DR PaxDb; P9WKD3; -.
DR DNASU; 888742; -.
DR GeneID; 45426045; -.
DR GeneID; 888742; -.
DR KEGG; mtu:Rv2068c; -.
DR TubercuList; Rv2068c; -.
DR eggNOG; COG2367; Bacteria.
DR OMA; EWMKGNA; -.
DR PhylomeDB; P9WKD3; -.
DR BRENDA; 3.5.2.6; 3445.
DR Proteomes; UP000001584; Chromosome.
DR GO; GO:0005576; C:extracellular region; IDA:MTBBASE.
DR GO; GO:0042597; C:periplasmic space; IEA:UniProtKB-SubCell.
DR GO; GO:0005886; C:plasma membrane; HDA:MTBBASE.
DR GO; GO:0008800; F:beta-lactamase activity; IDA:MTBBASE.
DR GO; GO:0033251; F:cephalosporinase activity; IDA:MTBBASE.
DR GO; GO:0033250; F:penicillinase activity; IDA:MTBBASE.
DR GO; GO:0030655; P:beta-lactam antibiotic catabolic process; IMP:MTBBASE.
DR GO; GO:0046677; P:response to antibiotic; IMP:MTBBASE.
DR Gene3D; 3.40.710.10; -; 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; PTHR35333; 1.
DR Pfam; PF13354; Beta-lactamase2; 1.
DR PRINTS; PR00118; BLACTAMASEA.
DR SUPFAM; SSF56601; SSF56601; 1.
DR PROSITE; PS00146; BETA_LACTAMASE_A; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Antibiotic resistance; Cell inner membrane; Cell membrane;
KW Hydrolase; Membrane; Periplasm; Reference proteome; Secreted; 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_0000017005"
FT ACT_SITE 84
FT /note="Acyl-ester intermediate"
FT /evidence="ECO:0000269|PubMed:19251630,
FT ECO:0000269|PubMed:20353175, ECO:0000269|PubMed:20961112"
FT ACT_SITE 182
FT /note="Proton acceptor"
FT /evidence="ECO:0000303|PubMed:20353175,
FT ECO:0000303|PubMed:20961112"
FT BINDING 142
FT /ligand="substrate"
FT /evidence="ECO:0000269|PubMed:19251630,
FT ECO:0000269|PubMed:20353175, ECO:0000269|PubMed:20961112"
FT BINDING 251..253
FT /ligand="substrate"
FT /evidence="ECO:0000269|PubMed:19251630,
FT ECO:0000269|PubMed:20353175, ECO:0000269|PubMed:20961112"
FT SITE 87
FT /note="Increases nucleophilicity of active site Ser"
FT /evidence="ECO:0000303|PubMed:20353175,
FT ECO:0000303|PubMed:20961112"
FT SITE 117
FT /note="Functions as a gatekeeper residue that regulates
FT substrate accessibility to the enzyme active site"
FT /evidence="ECO:0000303|PubMed:24023821"
FT MUTAGEN 8..9
FT /note="RR->KK: No longer exported via the Tat-system. Loss
FT of cell resistance to beta-lactam antibiotics."
FT /evidence="ECO:0000269|PubMed:16267291"
FT MUTAGEN 87
FT /note="K->A: 200000-fold decrease in catalytic efficiency
FT with cefamandole as substrate."
FT /evidence="ECO:0000269|PubMed:20961112"
FT MUTAGEN 117
FT /note="I->F: Significant increase in ampicillin resistance.
FT 2-fold and 3-fold increase in catalytic efficiency with
FT ampicillin and nitrocefin as substrate, respectively,
FT mainly due to an increase in substrate affinity."
FT /evidence="ECO:0000269|PubMed:24023821"
FT MUTAGEN 142
FT /note="S->G: Significant reduction of catalytic activity
FT for both nitrocefin and ampicillin. Leads to in vitro
FT clavulanate resistance and decreased susceptibility to
FT carbapenem inhibitors, but is still susceptible to
FT ampicillin-clavulanate in vivo."
FT /evidence="ECO:0000269|PubMed:24060876"
FT MUTAGEN 182
FT /note="E->A: Loss of catalytic activity with cefamandole as
FT substrate."
FT /evidence="ECO:0000269|PubMed:20961112"
FT MUTAGEN 236
FT /note="R->A,S: Significant reduction of catalytic activity
FT for both nitrocefin and ampicillin. Leads to in vitro
FT clavulanate resistance and decreased susceptibility to
FT carbapenem inhibitors, but is still susceptible to
FT ampicillin-clavulanate in vivo."
FT /evidence="ECO:0000269|PubMed:24060876"
FT MUTAGEN 253
FT /note="T->A: Significant reduction of catalytic activity
FT for both nitrocefin and ampicillin. Only minor impairment
FT of the inactivation by clavulanate. Larger increase in
FT resistance to carbapenems."
FT /evidence="ECO:0000269|PubMed:24060876"
FT MUTAGEN 253
FT /note="T->S: Only minor impairment of catalytic activity
FT with both nitrocefin and ampicillin. Still inhibited by
FT clavulanate and carbapenems."
FT /evidence="ECO:0000269|PubMed:24060876"
FT HELIX 45..55
FT /evidence="ECO:0007829|PDB:5NJ2"
FT STRAND 58..63
FT /evidence="ECO:0007829|PDB:5NJ2"
FT STRAND 67..69
FT /evidence="ECO:0007829|PDB:3NY4"
FT STRAND 72..75
FT /evidence="ECO:0007829|PDB:5NJ2"
FT HELIX 83..86
FT /evidence="ECO:0007829|PDB:5NJ2"
FT HELIX 87..97
FT /evidence="ECO:0007829|PDB:5NJ2"
FT HELIX 100..104
FT /evidence="ECO:0007829|PDB:5NJ2"
FT HELIX 111..113
FT /evidence="ECO:0007829|PDB:5NJ2"
FT HELIX 119..124
FT /evidence="ECO:0007829|PDB:5NJ2"
FT TURN 125..127
FT /evidence="ECO:0007829|PDB:5NJ2"
FT HELIX 131..140
FT /evidence="ECO:0007829|PDB:5NJ2"
FT HELIX 144..155
FT /evidence="ECO:0007829|PDB:5NJ2"
FT TURN 157..159
FT /evidence="ECO:0007829|PDB:5NJ2"
FT HELIX 160..170
FT /evidence="ECO:0007829|PDB:5NJ2"
FT HELIX 184..186
FT /evidence="ECO:0007829|PDB:5NJ2"
FT STRAND 194..197
FT /evidence="ECO:0007829|PDB:3VFH"
FT HELIX 199..210
FT /evidence="ECO:0007829|PDB:5NJ2"
FT STRAND 212..215
FT /evidence="ECO:0007829|PDB:5NJ2"
FT HELIX 217..228
FT /evidence="ECO:0007829|PDB:5NJ2"
FT TURN 234..236
FT /evidence="ECO:0007829|PDB:5NJ2"
FT HELIX 237..240
FT /evidence="ECO:0007829|PDB:5NJ2"
FT STRAND 245..254
FT /evidence="ECO:0007829|PDB:5NJ2"
FT TURN 255..257
FT /evidence="ECO:0007829|PDB:5NJ2"
FT STRAND 258..266
FT /evidence="ECO:0007829|PDB:5NJ2"
FT STRAND 272..280
FT /evidence="ECO:0007829|PDB:5NJ2"
FT HELIX 282..284
FT /evidence="ECO:0007829|PDB:5NJ2"
FT HELIX 292..307
FT /evidence="ECO:0007829|PDB:5NJ2"
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
