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Escherichia coli K-12 substr. MG1655 Enzyme: β-lactamase; penicillin resistance



Gene: ampC Accession Numbers: EG10040 (EcoCyc), b4150, ECK4146

Synonyms: ampA

Regulation Summary Diagram: ?

Summary:
The ampC β-lactamase gene encodes a serine cephalosporinase [Jaurin81]. AmpC was shown to be active against penicillin G with a Km of 12 μM, D-ampicillin with a Km of 6 μM, and cephalosporin C with a Km of 217 μM [Linstrom70]. AmpC has been shown to bind 125I-penicillin-X and aztreonam [Henderson97]. AmpC is also believed to have an additional function as a peptidoglycan hydrolyzing enzyme [Bishop93].

The ampA1 mutation, located in the promoter or operator region for ampC, causes increased expression of the ampC gene resulting in increased β-lactam resistance [ErikssonGrennbe65, Normark77, Grundstrom80].

ampC mutants exhibit aberrant cell morphology in a mrcA dacA background [Henderson97]. Overexpression of bolA increases ampC expression in addition to dacA and dacC expression [Santos02].

The structure of AmpC has been determined by X-ray crystallography to a resolution of 2.0 Å for the native enzyme and 2.3 Å as a complex with m-aminophenylboronic acid [Usher98].

Review: [Jacoby09].

Gene Citations: [Jaurin81a, Bishop95, Jaurin82]

Locations: periplasmic space

Map Position: [4,375,834 <- 4,376,967] (94.31 centisomes)
Length: 1134 bp / 377 aa

Molecular Weight of Polypeptide: 41.556 kD (from nucleotide sequence), 29 kD (experimental) [Linstrom70 ]

Unification Links: ASAP:ABE-0013592 , CGSC:1033 , EchoBASE:EB0038 , EcoGene:EG10040 , EcoliWiki:b4150 , ModBase:P00811 , OU-Microarray:b4150 , PortEco:ampC , PR:PRO_000022095 , Protein Model Portal:P00811 , RefSeq:NP_418574 , RegulonDB:EG10040 , SMR:P00811 , String:511145.b4150 , UniProt:P00811

Relationship Links: InterPro:IN-FAMILY:IPR001466 , InterPro:IN-FAMILY:IPR001586 , InterPro:IN-FAMILY:IPR012338 , PDB:Structure:1C3B , PDB:Structure:1FCM , PDB:Structure:1FCN , PDB:Structure:1FCO , PDB:Structure:1FSW , PDB:Structure:1FSY , PDB:Structure:1GA9 , PDB:Structure:1I5Q , PDB:Structure:1IEL , PDB:Structure:1IEM , PDB:Structure:1KDS , PDB:Structure:1KDW , PDB:Structure:1KE0 , PDB:Structure:1KE3 , PDB:Structure:1KE4 , PDB:Structure:1KVL , PDB:Structure:1KVM , PDB:Structure:1L0D , PDB:Structure:1L0E , PDB:Structure:1L0F , PDB:Structure:1L0G , PDB:Structure:1L2S , PDB:Structure:1LL5 , PDB:Structure:1LL9 , PDB:Structure:1LLB , PDB:Structure:1MXO , PDB:Structure:1MY8 , PDB:Structure:1O07 , PDB:Structure:1PI4 , PDB:Structure:1PI5 , PDB:Structure:1XGI , PDB:Structure:1XGJ , PDB:Structure:2BLS , PDB:Structure:2FFY , PDB:Structure:2HDQ , PDB:Structure:2HDR , PDB:Structure:2HDS , PDB:Structure:2HDU , PDB:Structure:2I72 , PDB:Structure:2P9V , PDB:Structure:2PU2 , PDB:Structure:2PU4 , PDB:Structure:2R9W , PDB:Structure:2R9X , PDB:Structure:2RCX , PDB:Structure:3BLS , PDB:Structure:3BM6 , PDB:Structure:3FKV , PDB:Structure:3FKW , PDB:Structure:3GQZ , PDB:Structure:3GR2 , PDB:Structure:3GRJ , PDB:Structure:3GSG , PDB:Structure:3GTC , PDB:Structure:3GV9 , PDB:Structure:3GVB , PDB:Structure:3IWI , PDB:Structure:3IWO , PDB:Structure:3IWQ , PDB:Structure:3IXB , PDB:Structure:3IXD , PDB:Structure:3IXG , PDB:Structure:3IXH , PDB:Structure:3O86 , PDB:Structure:3O87 , PDB:Structure:3O88 , PDB:Structure:4E3I , PDB:Structure:4E3J , PDB:Structure:4E3K , PDB:Structure:4E3L , PDB:Structure:4E3M , PDB:Structure:4E3N , PDB:Structure:4E3O , Pfam:IN-FAMILY:PF00144 , Prosite:IN-FAMILY:PS00336

In Paralogous Gene Group: 113 (2 members)

Gene-Reaction Schematic: ?

Genetic Regulation Schematic: ?

GO Terms:

Biological Process: GO:0017001 - antibiotic catabolic process Inferred by computational analysis [GOA01a]
GO:0046677 - response to antibiotic Inferred by computational analysis [UniProtGOA11a]
Molecular Function: GO:0008800 - beta-lactamase activity Inferred from experiment Inferred by computational analysis [GOA01, GOA01a, Henderson97]
GO:0016787 - hydrolase activity Inferred by computational analysis [UniProtGOA11a]
Cellular Component: GO:0030288 - outer membrane-bounded periplasmic space Inferred by computational analysis [GOA01a]
GO:0042597 - periplasmic space Inferred by computational analysis [UniProtGOA11, UniProtGOA11a]

MultiFun Terms: cell processes protection drug resistance/sensitivity
cell structure murein
metabolism biosynthesis of macromolecules (cellular constituents) murein (peptidoglycan)

Essentiality data for ampC knockouts: ?

Growth Medium Growth? T (°C) O2 pH Osm/L Growth Observations
LB enriched Yes 37 Aerobic 6.95   Yes [Gerdes03, Comment 1]
LB Lennox Yes 37 Aerobic 7   Yes [Baba06, Comment 2]
M9 medium with 1% glycerol Yes 37 Aerobic 7.2 0.35 Yes [Joyce06, Comment 3]
MOPS medium with 0.4% glucose Yes 37 Aerobic 7.2 0.22 Yes [Baba06, Comment 2]

Enzymatic reaction of: β-lactamase

Synonyms: β-lactamase, penicillinase, β-lactam hydrolase

EC Number: 3.5.2.6

a β-lactam[periplasmic space] + H2O[periplasmic space] <=> a substituted β-amino acid[periplasmic space]

The reaction direction shown, that is, A + B ↔ C + D versus C + D ↔ A + B, is in accordance with the direction of enzyme catalysis.

The reaction is physiologically favored in the direction shown.


Sequence Features

Feature Class Location Citations Comment
Signal-Sequence 1 -> 19
[Jaurin81]
 
Chain 20 -> 377
[UniProt09]
UniProt: Beta-lactamase;
Mutagenesis-Variant 80
[Beadle02, UniProt11a]
Alternate sequence: S → G; UniProt: Loss of activity.
Alternate sequence: S → E; UniProt: Loss of activity.
Alternate sequence: S → D; UniProt: Loss of activity.
Active-Site 80
[Jaurin81, UniProt11a]
UniProt: Acyl-ester intermediate.
Mutagenesis-Variant 83
[Beadle02, UniProt11a]
Alternate sequence: K → T; UniProt: Lowers activity more than 1000- fold and increases protein stability.
Alternate sequence: K → Q; UniProt: Lowers activity more than 1000- fold and increases protein stability.
Mutagenesis-Variant 166
[Beadle02, UniProt11a]
Alternate sequence: Y → E; UniProt: Lowers activity more than 1000- fold.
Active-Site 166
[UniProt10a]
UniProt: Proton acceptor;
Mutagenesis-Variant 168
[Beadle02, UniProt11a]
Alternate sequence: N → H; UniProt: Lowers activity more than 1000- fold.
Alternate sequence: N → D; UniProt: Lowers activity more than 1000- fold.
Mutagenesis-Variant 331
[Beadle02, UniProt11a]
Alternate sequence: K → A; UniProt: Lowers activity more than 1000- fold.
Protein-Segment 331 -> 333
[UniProt10]
UniProt: Substrate binding; Sequence Annotation Type: region of interest; Non-Experimental Qualifier: by similarity;


Gene Local Context (not to scale): ?

Transcription Unit:

Notes:

History:
10/20/97 Gene b4150 from Blattner lab Genbank (v. M52) entry merged into EcoCyc gene EG10040; confirmed by SwissProt match.


References

Baba06: Baba T, Ara T, Hasegawa M, Takai Y, Okumura Y, Baba M, Datsenko KA, Tomita M, Wanner BL, Mori H (2006). "Construction of Escherichia coli K-12 in-frame, single-gene knockout mutants: the Keio collection." Mol Syst Biol 2;2006.0008. PMID: 16738554

Beadle02: Beadle BM, Shoichet BK (2002). "Structural bases of stability-function tradeoffs in enzymes." J Mol Biol 321(2);285-96. PMID: 12144785

Bishop93: Bishop RE, Weiner JH (1993). "Complementation of growth defect in an ampC deletion mutant of Escherichia coli." FEMS Microbiol Lett 114(3);349-54. PMID: 8288112

Bishop95: Bishop RE, Penfold SS, Frost LS, Holtje JV, Weiner JH (1995). "Stationary phase expression of a novel Escherichia coli outer membrane lipoprotein and its relationship with mammalian apolipoprotein D. Implications for the origin of lipocalins." J Biol Chem 1995;270(39);23097-103. PMID: 7559452

ErikssonGrennbe65: Eriksson-Grennberg KG, Boman HG, Jansson JA, Thoren S (1965). "Resistance of Escherichia coli to Penicillins I. Genetic Study of Some Ampicillin-Resistant Mutants." J Bacteriol 90(1);54-62. PMID: 16562043

Gerdes03: Gerdes SY, Scholle MD, Campbell JW, Balazsi G, Ravasz E, Daugherty MD, Somera AL, Kyrpides NC, Anderson I, Gelfand MS, Bhattacharya A, Kapatral V, D'Souza M, Baev MV, Grechkin Y, Mseeh F, Fonstein MY, Overbeek R, Barabasi AL, Oltvai ZN, Osterman AL (2003). "Experimental determination and system level analysis of essential genes in Escherichia coli MG1655." J Bacteriol 185(19);5673-84. PMID: 13129938

GOA01: GOA, MGI (2001). "Gene Ontology annotation based on Enzyme Commission mapping." Genomics 74;121-128.

GOA01a: GOA, DDB, FB, MGI, ZFIN (2001). "Gene Ontology annotation through association of InterPro records with GO terms."

Grundstrom80: Grundstrom T, Jaurin B, Edlund T, Normark S (1980). "Physical mapping and expression of hybrid plasmids carrying chromosomal beta-lactamase genes of Escherichia coli K-12." J Bacteriol 143(3);1127-34. PMID: 6251026

Henderson97: Henderson TA, Young KD, Denome SA, Elf PK (1997). "AmpC and AmpH, proteins related to the class C beta-lactamases, bind penicillin and contribute to the normal morphology of Escherichia coli." J Bacteriol 179(19);6112-21. PMID: 9324260

Jacoby09: Jacoby GA (2009). "AmpC beta-lactamases." Clin Microbiol Rev 22(1);161-82, Table of Contents. PMID: 19136439

Jaurin81: Jaurin B, Grundstrom T (1981). "ampC cephalosporinase of Escherichia coli K-12 has a different evolutionary origin from that of beta-lactamases of the penicillinase type." Proc Natl Acad Sci U S A 78(8);4897-901. PMID: 6795623

Jaurin81a: Jaurin B, Grundstrom T, Edlund T, Normark S (1981). "The E. coli beta-lactamase attenuator mediates growth rate-dependent regulation." Nature 1981;290(5803);221-5. PMID: 7010184

Jaurin82: Jaurin B, Grundstrom T, Normark S (1982). "Sequence elements determining ampC promoter strength in E. coli." EMBO J 1(7);875-81. PMID: 6329713

Joyce06: Joyce AR, Reed JL, White A, Edwards R, Osterman A, Baba T, Mori H, Lesely SA, Palsson BO, Agarwalla S (2006). "Experimental and computational assessment of conditionally essential genes in Escherichia coli." J Bacteriol 188(23);8259-71. PMID: 17012394

KnottHunziker82: Knott-Hunziker V, Petursson S, Waley SG, Jaurin B, Grundstrom T (1982). "The acyl-enzyme mechanism of beta-lactamase action. The evidence for class C Beta-lactamases." Biochem J 207(2);315-22. PMID: 6818947

Linstrom70: Linstrom EB, Boman HG, Steele BB (1970). "Resistance of Escherichia coli to penicillins. VI. Purification and characterization of the chromosomally mediated penicillinase present in ampA-containing strains." J Bacteriol 101(1);218-31. PMID: 4983650

Normark77: Normark S, Burman LG (1977). "Resistance of Escherichia coli to penicillins: fine-structure mapping and dominance of chromosomal beta-lactamase mutations." J Bacteriol 132(1);1-7. PMID: 334718

Santos02: Santos JM, Lobo M, Matos AP, De Pedro MA, Arraiano CM (2002). "The gene bolA regulates dacA (PBP5), dacC (PBP6) and ampC (AmpC), promoting normal morphology in Escherichia coli." Mol Microbiol 45(6);1729-40. PMID: 12354237

UniProt09: UniProt Consortium (2009). "UniProt version 15.8 released on 2009-10-01 00:00:00." Database.

UniProt10: UniProt Consortium (2010). "UniProt version 2010-07 released on 2010-06-15 00:00:00." Database.

UniProt10a: UniProt Consortium (2010). "UniProt version 2010-11 released on 2010-11-02 00:00:00." Database.

UniProt11a: UniProt Consortium (2011). "UniProt version 2011-06 released on 2011-06-30 00:00:00." Database.

UniProtGOA11: UniProt-GOA (2011). "Gene Ontology annotation based on the manual assignment of UniProtKB Subcellular Location terms in UniProtKB/Swiss-Prot entries."

UniProtGOA11a: UniProt-GOA (2011). "Gene Ontology annotation based on manual assignment of UniProtKB keywords in UniProtKB/Swiss-Prot entries."

Usher98: Usher KC, Blaszczak LC, Weston GS, Shoichet BK, Remington SJ (1998). "Three-dimensional structure of AmpC beta-lactamase from Escherichia coli bound to a transition-state analogue: possible implications for the oxyanion hypothesis and for inhibitor design." Biochemistry 37(46);16082-92. PMID: 9819201

Other References Related to Gene Regulation

Tracz07: Tracz DM, Boyd DA, Hizon R, Bryce E, McGeer A, Ofner-Agostini M, Simor AE, Paton S, Mulvey MR, (2007). "ampC gene expression in promoter mutants of cefoxitin-resistant Escherichia coli clinical isolates." FEMS Microbiol Lett 270(2);265-71. PMID: 17326753


Report Errors or Provide Feedback
Please cite the following article in publications resulting from the use of EcoCyc: Nucleic Acids Research 41:D605-12 2013
Page generated by SRI International Pathway Tools version 18.5 on Sat Dec 20, 2014, BIOCYC13B.