{"entryType":"UniProtKB reviewed (Swiss-Prot)","primaryAccession":"Q6XEC0","uniProtkbId":"BLO48_KLEPN","entryAudit":{"firstPublicDate":"2025-02-05","lastAnnotationUpdateDate":"2026-06-10","lastSequenceUpdateDate":"2004-07-05","entryVersion":137,"sequenceVersion":1},"annotationScore":5.0,"organism":{"scientificName":"Klebsiella pneumoniae","taxonId":573,"evidences":[{"evidenceCode":"ECO:0000312","source":"EMBL","id":"AAP70012.1"}],"lineage":["Bacteria","Pseudomonadati","Pseudomonadota","Gammaproteobacteria","Enterobacterales","Enterobacteriaceae","Klebsiella/Raoultella group","Klebsiella","Klebsiella pneumoniae complex"]},"proteinExistence":"1: Evidence at protein level","proteinDescription":{"recommendedName":{"fullName":{"evidences":[{"evidenceCode":"ECO:0000255","source":"RuleBase","id":"RU361140"},{"evidenceCode":"ECO:0000303","source":"PubMed","id":"14693513"}],"value":"Beta-lactamase OXA-48"},"ecNumbers":[{"evidences":[{"evidenceCode":"ECO:0000255","source":"RuleBase","id":"RU361140"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"14693513"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"19477418"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"27073009"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"38161376"}],"value":"3.5.2.6"}]},"flag":"Precursor"},"genes":[{"geneName":{"evidences":[{"evidenceCode":"ECO:0000303","source":"PubMed","id":"14693513"}],"value":"OXA-48"},"synonyms":[{"evidences":[{"evidenceCode":"ECO:0000312","source":"EMBL","id":"AAP70012.1"}],"value":"bla OXA-48"},{"evidences":[{"evidenceCode":"ECO:0000312","source":"EMBL","id":"SWV87943.1"}],"value":"bla_4"},{"evidences":[{"evidenceCode":"ECO:0000303","source":"PubMed","id":"14693513"},{"evidenceCode":"ECO:0000312","source":"EMBL","id":"AEV46197.1"}],"value":"blaOXA-48"}],"orfNames":[{"evidences":[{"evidenceCode":"ECO:0000312","source":"EMBL","id":"AGW25497.1"}],"value":"KPE71T_00045"},{"evidences":[{"evidenceCode":"ECO:0000312","source":"EMBL","id":"SWV87943.1"}],"value":"SAMEA3727706_05517"}]}],"comments":[{"texts":[{"evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"14693513"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"19477418"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"27073009"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"38161376"}],"value":"Class D beta-lactamase which confers resistance to the beta-lactam antibiotics, including amoxicillin, and moderate resistance to cephalosporins and carbapenems such as cephalothin and imipenem; in the DH10B strain of E.coli (PubMed:14693513). Acts via hydrolysis of the beta-lactam ring (PubMed:14693513, PubMed:19477418, PubMed:27073009, PubMed:38161376). Has oxacillin-, cephalothin- and imipenem-hydrolyzing activities (PubMed:14693513, PubMed:19477418, PubMed:27073009, PubMed:38161376)"}],"commentType":"FUNCTION"},{"commentType":"CATALYTIC ACTIVITY","reaction":{"name":"a beta-lactam + H2O = a substituted beta-amino acid","reactionCrossReferences":[{"database":"Rhea","id":"RHEA:20401"},{"database":"ChEBI","id":"CHEBI:15377"},{"database":"ChEBI","id":"CHEBI:35627"},{"database":"ChEBI","id":"CHEBI:140347"}],"ecNumber":"3.5.2.6","evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"14693513"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"19477418"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"27073009"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"38161376"}]}},{"texts":[{"evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"14693513"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"25406838"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"26731698"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"32150407"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"38161376"}],"value":"Inhibited by avibactam, related diazabicyclooctane (DBO) derivatives and by bicyclic boronic acids, via a covalent binding to Ser-70 (PubMed:25406838, PubMed:26731698, PubMed:32150407). Inhibited by chloride, bromide and iodide ions (PubMed:38161376). Not inhibited by the beta-lactamase-blocking agents, clavulanic acid or tazobactam (PubMed:14693513)"}],"commentType":"ACTIVITY REGULATION"},{"commentType":"BIOPHYSICOCHEMICAL PROPERTIES","kineticParameters":{"michaelisConstants":[{"constant":40.0,"unit":"uM","substrate":"benzylpenicillin (at pH 7.0 and 30 degrees Celsius)","evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"14693513"}]},{"constant":5200.0,"unit":"uM","substrate":"ampicillin (at pH 7.0 and 30 degrees Celsius)","evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"14693513"}]},{"constant":1630.0,"unit":"uM","substrate":"ampicillin (at pH 7.2 and 30 degrees Celsius)","evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"27073009"}]},{"constant":395.0,"unit":"uM","substrate":"ampicillin (at pH 7.0)","evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"19477418"}]},{"constant":45.0,"unit":"uM","substrate":"temocillin (at pH 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7.0)","evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"19477418"}]},{"constant":200.0,"unit":"uM","substrate":"cefoxitin (at pH 7.0)","evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"19477418"}]},{"constant":27.0,"unit":"uM","substrate":"cephaloridine (at pH 7.0 and 30 degrees Celsius)","evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"14693513"}]},{"constant":190.0,"unit":"uM","substrate":"cefotaxime (at pH 7.0 and 30 degrees Celsius)","evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"14693513"}]},{"constant":900.0,"unit":"uM","substrate":"cefotaxime (at pH 7.0)","evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"19477418"}]},{"constant":5100.0,"unit":"uM","substrate":"ceftazidime (at pH 7.0 and 30 degrees Celsius)","evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"14693513"}]},{"constant":160.0,"unit":"uM","substrate":"cefepime (at pH 7.0 and 30 degrees Celsius)","evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"14693513"}]},{"constant":550.0,"unit":"uM","substrate":"cefepime (at pH 7.0)","evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"19477418"}]},{"constant":390.0,"unit":"uM","substrate":"cefpirome (at pH 7.0 and 30 degrees Celsius)","evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"14693513"}]},{"constant":30.0,"unit":"uM","substrate":"oxacillin (at pH 7.0 and 30 degrees Celsius)","evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"14693513"}]},{"constant":95.0,"unit":"uM","substrate":"oxacillin (at pH 7.0)","evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"19477418"}]},{"constant":14.0,"unit":"uM","substrate":"imipenem (at pH 7.0 and 30 degrees Celsius)","evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"14693513"}]},{"constant":13.0,"unit":"uM","substrate":"imipenem (at pH 7.0)","evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"19477418"}]},{"constant":200.0,"unit":"uM","substrate":"meropenem (at pH 7.0 and 30 degrees Celsius)","evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"14693513"}]},{"constant":11.0,"unit":"uM","substrate":"meropenem (at pH 7.0)","evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"19477418"}]},{"constant":100.0,"unit":"uM","substrate":"ertapenem (at pH 7.0)","evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"19477418"}]},{"constant":14.0,"unit":"uM","substrate":"panipenem (at pH 7.0)","evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"19477418"}]},{"constant":13.0,"unit":"uM","substrate":"faropenem (at pH 7.0)","evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"19477418"}]}],"note":{"texts":[{"evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"14693513"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"19477418"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"27073009"}],"value":"kcat is 245 sec(-1) with benzylpenicillin as substrate (at pH 7.0 and 30 degrees Celsius) (PubMed:14693513). kcat is 340 sec(-1) with ampicillin as substrate (at pH 7.0 and 30 degrees Celsius) (PubMed:14693513). kcat is 208 sec(-1) with ampicillin as substrate (at pH 7.2 and 30 degrees Celsius) (PubMed:27073009). kcat is 955 sec(-1) with ampicillin as substrate (at pH 7.0) (PubMed:19477418). kcat is 0.3 sec(-1) with temocillin as substrate (at pH 7.0) (PubMed:19477418). kcat is 45 sec(-1) with ticarcillin as substrate (at pH 7.0 and 30 degrees Celsius) (PubMed:14693513). kcat is 75 sec(-1) with piperacillin as substrate (at pH 7.0 and 30 degrees Celsius) (PubMed:14693513). kcat is 940 sec(-1) with nitrocefin as substrate (at pH 7.0) (PubMed:19477418). kcat is 3 sec(-1) with cephalothin as substrate (at pH 7.0 and 30 degrees Celsius) (PubMed:14693513). kcat is 2.8 sec(-1) with cephalothin as substrate (at pH 7.2 and 30 degrees Celsius) (PubMed:27073009). kcat is 0.05 sec(-1) with cefoxitin as substrate (at pH 7.0) (PubMed:19477418). kcat is 44 sec(-1) with cephalothin as substrate (at pH 7.0) (PubMed:19477418). kcat is 2 sec(-1) with cephaloridine as substrate (at pH 7.0 and 30 degrees Celsius) (PubMed:14693513). kcat is 10 sec(-1) with cefotaxime as substrate (at pH 7.0 and 30 degrees Celsius) (PubMed:14693513). kcat is 9 sec(-1) with cefotaxime as substrate (at pH 7.0) (PubMed:19477418). kcat is 4 sec(-1) with ceftazidime as substrate (at pH 7.0 and 30 degrees Celsius) (PubMed:14693513). kcat is 1 sec(-1) with cefepime as substrate (at pH 7.0 and 30 degrees Celsius) (PubMed:14693513). kcat is 0.6 sec(-1) with cefepime as substrate (at pH 7.0) (PubMed:19477418). kcat is 8 sec(-1) with cefpirome as substrate (at pH 7.0 and 30 degrees Celsius) (PubMed:14693513). kcat is 25 sec(-1) with oxacillin as substrate (at pH 7.0 and 30 degrees Celsius) (PubMed:14693513). kcat is 130 sec(-1) with oxacillin as substrate (at pH 7.0) (PubMed:19477418). kcat is 2 sec(-1) with imipenem as substrate (at pH 7.0 and 30 degrees Celsius) (PubMed:14693513). kcat is 4.8 sec(-1) with imipenem as substrate (at pH 7.0) (PubMed:19477418). kcat is 0.1 sec(-1) with meropenem as substrate (at pH 7.0 and 30 degrees Celsius) (PubMed:14693513). kcat is 0.07 sec(-1) with meropenem as substrate (at pH 7.0) (PubMed:19477418). kcat is 0.13 sec(-1) with ertapenem as substrate (at pH 7.0) (PubMed:19477418). kcat is 1.4 sec(-1) with panipenem as substrate (at pH 7.0) (PubMed:19477418). kcat is 0.04 sec(-1) with faropenem as substrate (at pH 7.0) (PubMed:19477418)."}]}}},{"texts":[{"evidences":[{"evidenceCode":"ECO:0000250","source":"UniProtKB","id":"P13661"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"30153368"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"31358584"}],"value":"Monomer (By similarity). Dimer (PubMed:30153368, PubMed:31358584)"}],"commentType":"SUBUNIT"},{"texts":[{"evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"14693513"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"16952941"}],"value":"Expressed from an upstream promoter, P(out), in an insertion sequence IS1999"}],"commentType":"INDUCTION"},{"texts":[{"evidences":[{"evidenceCode":"ECO:0000250","source":"UniProtKB","id":"Q8RLA6"},{"evidenceCode":"ECO:0000250","source":"UniProtKB","id":"Q9L4P2"}],"value":"Carboxylated on the epsilon-amino group of a lysine, with the resulting carbamate functional group serving as a general base (By similarity). Probably N-carboxylated at Lys-73 at neutral pH in vivo and undergoes complete N-decarboxylation, at pH 4.1, in vitro (By similarity)"}],"commentType":"PTM"},{"texts":[{"evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"38161376"}],"value":"When OXA-48 is present in clinical isolates of K.pneumoniae, increasing chloride concentration during antibiotic treatment reduces bacterial growth"}],"commentType":"MISCELLANEOUS"},{"texts":[{"evidences":[{"evidenceCode":"ECO:0000305"}],"value":"Belongs to the class-D beta-lactamase family"}],"commentType":"SIMILARITY"}],"features":[{"type":"Signal","location":{"start":{"value":1,"modifier":"EXACT"},"end":{"value":22,"modifier":"EXACT"}},"description":"","evidences":[{"evidenceCode":"ECO:0000255"}]},{"type":"Chain","location":{"start":{"value":23,"modifier":"EXACT"},"end":{"value":265,"modifier":"EXACT"}},"description":"Beta-lactamase OXA-48","evidences":[{"evidenceCode":"ECO:0000255"}],"featureId":"PRO_5015098593"},{"type":"Active site","location":{"start":{"value":70,"modifier":"EXACT"},"end":{"value":70,"modifier":"EXACT"}},"description":"Acyl-ester intermediate","evidences":[{"evidenceCode":"ECO:0000255","source":"PIRSR","id":"PIRSR602137-50"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"25406838"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"26731698"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"31358584"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"32150407"},{"evidenceCode":"ECO:0007744","source":"PDB","id":"4WMC"},{"evidenceCode":"ECO:0007744","source":"PDB","id":"5FAQ"},{"evidenceCode":"ECO:0007744","source":"PDB","id":"5FAS"},{"evidenceCode":"ECO:0007744","source":"PDB","id":"6P97"},{"evidenceCode":"ECO:0007744","source":"PDB","id":"6P98"},{"evidenceCode":"ECO:0007744","source":"PDB","id":"6P99"},{"evidenceCode":"ECO:0007744","source":"PDB","id":"6P9C"},{"evidenceCode":"ECO:0007744","source":"PDB","id":"6V1O"}]},{"type":"Binding site","location":{"start":{"value":70,"modifier":"EXACT"},"end":{"value":70,"modifier":"EXACT"}},"description":"","featureCrossReferences":[{"database":"ChEBI","id":"CHEBI:35627"}],"evidences":[{"evidenceCode":"ECO:0000250","source":"UniProtKB","id":"Q8RLA6"}],"ligand":{"name":"a beta-lactam","id":"ChEBI:CHEBI:35627"}},{"type":"Binding site","location":{"start":{"value":73,"modifier":"EXACT"},"end":{"value":73,"modifier":"EXACT"}},"description":"","featureCrossReferences":[{"database":"ChEBI","id":"CHEBI:35627"}],"evidences":[{"evidenceCode":"ECO:0000250","source":"UniProtKB","id":"P13661"}],"ligand":{"name":"a beta-lactam","id":"ChEBI:CHEBI:35627"}},{"type":"Binding site","location":{"start":{"value":118,"modifier":"EXACT"},"end":{"value":118,"modifier":"EXACT"}},"description":"","featureCrossReferences":[{"database":"ChEBI","id":"CHEBI:35627"}],"evidences":[{"evidenceCode":"ECO:0000250","source":"UniProtKB","id":"Q8RLA6"}],"ligand":{"name":"a beta-lactam","id":"ChEBI:CHEBI:35627"}},{"type":"Binding site","location":{"start":{"value":250,"modifier":"EXACT"},"end":{"value":250,"modifier":"EXACT"}},"description":"","featureCrossReferences":[{"database":"ChEBI","id":"CHEBI:35627"}],"evidences":[{"evidenceCode":"ECO:0000250","source":"UniProtKB","id":"Q8RLA6"}],"ligand":{"name":"a beta-lactam","id":"ChEBI:CHEBI:35627"}},{"type":"Modified residue","location":{"start":{"value":73,"modifier":"EXACT"},"end":{"value":73,"modifier":"EXACT"}},"description":"N6-carboxylysine","evidences":[{"evidenceCode":"ECO:0000255","source":"PIRSR","id":"PIRSR602137-50"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"19477418"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"25406838"},{"evidenceCode":"ECO:0007744","source":"PDB","id":"3HBR"},{"evidenceCode":"ECO:0007744","source":"PDB","id":"4WMC"}]},{"type":"Mutagenesis","location":{"start":{"value":70,"modifier":"EXACT"},"end":{"value":70,"modifier":"EXACT"}},"description":"Does not alter thermal stability.","evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"27073009"}],"alternativeSequence":{"originalSequence":"S","alternativeSequences":["A"]}},{"type":"Mutagenesis","location":{"start":{"value":70,"modifier":"EXACT"},"end":{"value":70,"modifier":"EXACT"}},"description":"Increases thermal stability. 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Significantly decreases thermal stability; when associated with A-206.","evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"30153368"}],"alternativeSequence":{"originalSequence":"R","alternativeSequences":["A"]}},{"type":"Mutagenesis","location":{"start":{"value":206,"modifier":"EXACT"},"end":{"value":206,"modifier":"EXACT"}},"description":"No significant effect on catalytic efficiency with respect to ampicillin, nitrocefin or imipenem. Very little reduction in dimerization at neutral pH. Predominantly monomer at neutral pH; when associated with A-189. Slightly decreases thermal stability. Significantly decreases thermal stability; when associated with A-189.","evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"30153368"}],"alternativeSequence":{"originalSequence":"R","alternativeSequences":["A"]}},{"type":"Beta 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