Beta-lactamase

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[[Image:3bm6.png|left|200px|thumb|Crystal Structure of Beta-lactamase, [[3bm6]]]]
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<StructureSection load='' size='350' side='right' scene='45/453531/Cv/1' caption='Class B β-lactamase Ndm-1 complex with Zn+2 (grey) (PDB code [[3spu]])'>
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{{STRUCTURE_3bm6| PDB=3bm6 | SIZE=400| SCENE=Beta-lactamase/Beta-lactamase/1|right|CAPTION=Beta-lactamase class D dimer complex with boronic acid derivative, [[3bm6]] }}
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__TOC__
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== Function ==
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'''Beta-lactamase''' (Blac) are enzymes which make bacteria resistant to β-lactam antibiotics by breaking their β-lactam ring. Blac are classified according to their resistance targets. Class C are cephalosporinases; Class A are broad-spectrum; Class B are metalloenzymes; Class D are cloxacilanases. Carbapenemase (Car) are Blac with wide hydrolytic capacities. Car can hydrolyze penicillins, cephalosporins, monobactams and carbapenems. Extended-spectrum Blac (ESBL) hydrolyze penicillins but not cephalosporins.
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{{TOC limit|limit=2}}
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'''Beta-lactamase''' (Blac) are enzymes which make bacteria resistant to β-lactam antibiotics by breaking their β-lactam ring. Blac are classified according to their resistance targets.<br />
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*'''Class A''' are broad-spectrum. See also [[TEM1 Class Antibiotic Resistance Proteins]].<br />
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*'''Class B''' are metalloenzymes. See also [[New Delhi metallo-β-lactamase 1]].<br />
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*'''Class C''' are cephalosporinases. See also [[Class C beta-lactamase]].<br />
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*'''Class D''' are cloxacilanases<br />
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*'''Carbapenemase''' (Car) are Blac with wide hydrolytic capacities. Car can hydrolyze penicillins, cephalosporins, monobactams and carbapenems. <br />
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*'''Extended-spectrum Blac''' class A (ESBL) hydrolyze penicillins but not cephalosporins.<br />
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*'''Serine beta-lactamase''' (ClbP) has a serine-active site.
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*'''AmpC beta-lactamase''' (ClbP) mediate resistance to cephalosphin, cefazolin,cefoxitin and most penicillins<ref>PMID:19136439</ref>.
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== Relevance ==
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Blac makes some bacteria resistant to antibiotics like penicillin, cephamycin and carbapenems.
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== Structural highlights ==
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The <scene name='45/453531/Cv/3'>active site of class B Blac contains 2 Zn+2 ions</scene>.<ref>PMID:21774017</ref>
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==See also==
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[[Journal:Structure:1]]
== 3D Structures of Beta-lactamase ==
== 3D Structures of Beta-lactamase ==
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[[Beta-lactamase 3D structures]]
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''Update January 2013''
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</StructureSection>
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===β-lactamase class A===
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[[3dtm]], [[1bza]], [[1ck3]], [[1esu]], [[1jwp]], [[1lhy]], [[1li0]], [[1m40]], [[1zg6]], [[2v1z]], [[2v20]], [[3cmz]], [[3jyi]] - EcBlac A Tem-1 (mutant) - ''Escherichia coli''<br />
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[[1btl]], [[1iys]], [[1xpb]], [[1zg4]], [[4gku]] - EcBlac A Tem-1<br />
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[[1lhy]] - EcBlac A Tem-30 (mutant) <br />
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[[1li0]] - EcBlac A Tem-32 (mutant) <br />
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[[1li9]] - EcBlac A Tem-34 (mutant) <br />
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[[1yt4]] - EcBlac A Tem-76 (mutant) <br />
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[[3toi]] - EcBlac A Tem-116 (mutant)<br />
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[[1we4]], [[2xr0]], [[2zq7]], [[2zq8]], [[2zq9]], [[2zqa]], [[2zqc]], [[2zqd]] - EcBlac A Toho-1 (mutant) <br />
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[[2xqz]], [[2wyx]] - EcBlac A Toho-1 (mutant) – Neutron<br />
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[[3c5a]] – EcBlac A Kpc-2<br />
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[[1ylj]], [[1ylp]], [[1ylt]], [[1ylw]], [[1yly]], [[1ylz]], [[1ym1]], [[1yms]], [[1ymx]], [[2p74]] – EcBlac A Ctx-M<br />
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[[3hre]] - EcBlac A Ctx-M (mutant) <br />
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[[1o7e]], [[1n4o]] – StmBlac A – ''Stenotrophonas maltophilia''<br />
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[[1htz]] – KpBlac A Tem-52 – ''Klebsiella pneumoniae''<br />
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[[1shv]], [[4fh4]] - KpBlac A Shv-1<br />
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[[1tdl]], [[2a3u]], [[3oph]], [[3opl]], [[3v50]], [[3v5m]], [[4fd8]] - KpBlac A Shv-1 (mutant) <br />
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[[1n9b]] – KpBlac A Shv-2<br />
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[[2qpn]] – KpBlac A Ges-1<br />
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[[3ni9]] - PaBlac A Ges-2<br />
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[[1hzo]] – Blac A – ''Proteus vulgaris''<br />
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[[1kge]], [[1kgf]], [[1kgg]], [[1ome]]– SaBlac A (mutant) - S''taphylococcus aureus''<br />
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[[3blm]] – SaBlac A<br />
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[[1mbl]], [[3ly3]], [[3soi]] – BlBlac A (mutant) – ''Bacillus licheniformis''<br />
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[[2blm]], [[3sh7]] – BlBlac A<br />
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[[2cc1]] – Blac A – ''Mycobacterium fortuitum''<br />
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[[3bfd]], [[3bfe]] – CsBlac A Sed-1 (mutant) - ''Citrobacter sedlakii''
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===β-lactamase class A binary complex===
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[[1axb]] - EcBlac A (mutant) + transition state analog<br />
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[[1tem]], [[1bt5]], [[1fqg]], [[1iyo]], [[1iyp]], [[1iyq]], [[1jvj]], [[3q07]], [[3q1f]] - EcBlac A (mutant) + antibiotic<br />
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[[1nxy]], [[1ny0]], [[1nym]], [[1nyy]] - EcBlac A (mutant) + boronic acid inhibitor<br />
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[[1pzo]], [[1pzp]] - EcBlac A Tem-1 (mutant) + inhibitor<br />
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[[1erm]], [[1ero]], [[1erq]] – EcBlac A Tem-1 + boronic acid inhibitor<br />
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[[3g2y]], [[3g2z]], [[3g30]], [[3g31]], [[3g32]], [[3g34]], [[3g35]], [[4dds]], [[4ddy]], [[4de0]], [[4de1]], [[4de2]], [[4de3]] - EcBlac A Ctx-M + inhibitor<br />
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[[3hlw]], [[3huo]], [[3hvf]] - EcBlac A Ctx-M (mutant) + antibiotic<br />
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[[1jwv]], [[1jwz]] - EcBlac A Tem-1 (mutant) + boronic acid inhibitor<br />
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[[1ong]], [[1q2p]], [[1vm1]], [[2h5s]], [[2zd8]], [[3d4f]], [[3mke]], [[3mkf]], [[3mxr]], [[3mxs]], [[4fh2]] - KpBlac A Shv-1 + inhibitor<br />
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[[1rcj]], [[1tdg]], [[2a49]], [[2h0t]], [[2h0y]], [[2h10]] - KpBlac A Shv-1 (mutant) + inhibitor<br />
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[[3opp]], [[3opr]]- KpBlac A Shv-1 (mutant) + antibiotic<br />
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[[1w7f]], [[3b3x]], [[2y91]], [[4a5r]] - BlBlac A + inhibitor<br />
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[[3m2j]] - BlBlac A (mutant) + inhibitor<br />
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[[2wk0]], [[2x71]]– BlBlac A + antibiotic<br />
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[[3ly4]], [[3m2k]], [[3sh8]], [[3sh9]] - BlBlac A (mutant) + antibiotic<br />
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[[2q9m]], [[2q9n]] - EncBlac A + inhibitor – ''Enterobacter cloacae''<br />
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[[3bfc]], [[3bff]], [[3bfg]] – CsBlac A Sed-1 (mutant) + inhibitor<br />
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[[3nia]] - PaBlac A Ges-2 + inhibitor<br />
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[[3p98]] – Blac Tem-72 + citrate – ''Morganella morganii''
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===β-lactamase class A complex with β-lactamase inhibitor protein (Blip)===
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[[3c7u]], [[3c7v]], [[1jtg]], [[2b5r]] – EcBlac A (mutant) + Protein Blip<br />
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[[1jtd]], [[3gmw]] - EcBlac A + Protein Blip<br />
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[[1s0w]], [[1xxm]] - EcBlac A + Protein Blip (mutant) <br />
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[[2g2u]] - KpBlac A Shv-1 + Protein Blip<br />
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[[2g2w]], [[3n4i]] - KpBlac A Shv-1 (mutant) + Protein Blip<br />
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[[3c4o]], [[3c4p]] - KpBlac A Shv-1 + Protein Blip (mutant) <br />
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[[3e2k]], [[3e2l]] - KpBlac A Kpc-2 (mutant) + Protein Blip<br />
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[[3qhv]], [[2qhy]] - Blac A + Protein Blip – ''Bacillus anthracis''
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===β-lactamase class B (Zn containing)===
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[[3fcz]], [[3i0v]], [[3i11]], [[3i13]], [[3i14]], [[3i15]], [[1bc2]], [[1bvt]], [[1mqo]], [[2bc2]], [[3bc2]], [[1bmc]] – BcBlac B - ''Bacillus cereus''<br />
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[[3knr]], [[3kns]], [[1dxk]], [[2bfk]], [[2bfl]], [[2bfz]], [[2bg2]], [[2bg6]], [[2bg7]], [[2bg8]], [[2bga]], [[2nxa]], [[2nyp]], [[2nze]], [[2nzf]], [[2uyx]] - BcBlac B (mutant) <br />
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[[1a7t]], [[1znb]], [[2bmi]] – BfBlac B – ''Bacterioides fragilis''<br />
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[[2znb]] - BfBlac B (Cd) <br />
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[[3znb]] – BfBlac B (Zn, Hg) <br />
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[[4znb]] - BfBlac B (mutant) <br />
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[[1k07]] – FgBlac B]] - ''Fluoribacter gormanii''<br />
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[[1l9y]] - FgBlac B (mutant) <br />
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[[1ko2]], [[1ko3]] – PaBlac B Vim-2 - ''Pseudomonas aeruginosa''<br />
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[[2whg]], [[2wrs]] - PaBlac B Vim-4<br />
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[[4awy]], [[4awz]] - PaBlac B Aim-1<br />
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[[4ax0]], [[4ax1]] - PaBlac B Aim-1 (mutant)<br />
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[[2y87]], [[2y8a]], [[2y8b]] - PaBlac B Vim-7<br />
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[[2fhx]] - PaBlac B Spm-1<br />
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[[2x01]] - PaBlac Oxa-10 (mutant)<br />
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[[2x02]] - PaBlac Oxa-10<br />
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[[1wuo]], [[1wup]] - SmBlac Imp-1 (mutant) – ''Serratia marcescens''<br />
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[[2dkf]], [[2zo4]], [[2zwr]] – TtBlac B – ''Thermus thermophilus''<br />
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[[2zzi]] – TtBlac B (Fe) <br />
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[[2fm6]], [[2fu6]], [[2fu7]], [[2h6a]] – StmMlac B<br />
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[[2qin]], [[2qjs]] - StmBlac B (mutant) <br />
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[[2gmn]], [[3lvz]] – BjBlac B – ''Bradyrhizobium japonicum''<br />
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[[2p4z]] – Blac B – ''Thermoanaerobacter tengcongensis''<br />
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[[3l6n]] – Blac B – ''Chryseobacter indolegenes''<br />
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[[3r2u]] – SaBlac B<br />
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[[3rkj]], [[3sbl]], [[3sfp]], [[3spu]], [[3zr9]] - KpBlac B Ndm-1<br />
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[[3srx]] - KpBlac B Ndm-1 (Cd) <br />
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[[4h0d]] - KpBlac B Ndm-1 (Mn)<br />
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[[3rkk]], [[4gyq]], [[4gyu]] - KpBlac B Ndm-1 (mutant) <br />
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[[3s0z]] - EcBlac B Ndm-1<br />
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[[2yz3]] – Blac Vim-2 – ''Pseudomonas putida''<br />
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[[3sd9]] – SfBlac B - ''Serratia fonticola''<br />
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[[3pg4]] – KpBlac Ndm-1
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===β-lactamase class B binary complex===
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[[1a8t]], [[1hlk]], [[1kr3]] - BfBlac B + inhibitor<br />
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[[1jt1]] – FgBlac + captopril <br />
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[[1jje]], [[1jjt]], [[3lce]] - PaBlac B + inhibitor<br />
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[[1m2x]] – Blac B + captopril – ''Elizabethkingia meningoseptica''<br />
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[[1vgn]] - SmBlac Imp-1+ inhibitor<br />
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[[2doo]] - SmBlac Imp-1+ fluorescent agent<br />
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[[2aio]] – StmBlac B + antibiotic<br />
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[[2fu8]], [[2fu9]], [[2gfj]], [[2gfk]], [[2hb9]], [[2qdt]] - StmBlac B + inhibitor<br />
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[[3iof]], [[1x8i]], [[3iog]]– AhBlac B (mutant) + inhibitor<br />
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[[1x8g]], [[2gkl]] – AhBlac B + inhibitor<br />
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[[2qds]] – AhBlac B + captopril<br />
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[[3m8t]] – BjBlac B + inhibitor<br />
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[[3q6v]] – SfBlac B + glycerol <br />
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[[3q6x]], [[4ey2]], [[4eyb]], [[4eyf]], [[4efl]], [[4hl1]], [[4hl2]] – KpBlac B Ndm-1+ antibiotic<br />
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[[4exy]] – KpBlac B Ndm-1+ inhibitor
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===β-lactamase class C===
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[[3fkw]], [[3iwi]], [[3iwo]], [[3iwq]], [[3ixd]] – EcBlac C (mutant) <br />
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[[1zkj]] – Blac C – ''Enterobacter aerogenes''<br />
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[[2qz6]] – Blac C – ''Pseudomonas fluorescens''
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===β-lactamase class C binary complex===
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[[3bm6]], [[3fkv]], [[3o86]], [[3o87]], [[3o88]] – EcBlac C + boronic acid inhibitor<br />
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[[3ixb]], [[3ixg]] - EcBlac C (mutant) + boronic acid inhibitor<br />
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[[3ixh]] - EcBlac C (mutant) + cefotaxime<br />
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[[3gqz]], [[3gr2]], [[3grj]], [[3gsg]], [[3gtc]], [[3gv9]], [[3gvb]] - EcBlac C + inhibitor<br />
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[[1onh]], [[1q2q]], [[1y54]] - EncBlac C + inhibitor<br />
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[[1s6r]] - EncBlac C+ boronic acid inhibitor<br />
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[[1rgz]] - EncBlac C + antribiotic<br />
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[[1rgy]] - CfBlac C + antribiotic – ''Citrobacter freundii''<br />
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[[1zc2]], [[2zc7]] – KpBlac C + inhibitor<br />
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[[2wzx]], [[2wzz]] – PaBlac C + inhibitor<br />
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===β-lactamase class D===
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[[2rl3]], [[1k55]], [[1k57]], [[1k4e]], [[1ewz]], [[1fof]], [[1ddk]], [[1e3u]], [[1e4d]], [[1h8z]] – PaBlac D <br />
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[[2hp5]], [[2hp6]], [[2hp9]], [[2hpb]], [[2wgw]], [[2wki]] - PaBlac D (mutant) <br />
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[[1k56]], [[2k02]] - PaBlac Pse-2<br />
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[[1g68]], [[1k4f]] – PaBlac Pse-4<br />
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[[1g6a]] – PaBlac Pse-4 (mutant) <br />
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[[1ko2]] – PaBlac Vim-2<br />
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[[1k38]] – Blac D – ''Salmonella typhimurium''<br />
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[[1m6k]] – EcBlac D<br />
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[[3hbr]] – KpBlac D Oxa-48<br />
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[[3if6]] - KpBlac D Oxa-46
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===β-lactamase class D binary complex===
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[[1k6r]], [[1k54]] - PaBlac D + antibiotic<br />
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[[2wgi]], [[2wkh]] - PaBlac D (mutant) + antibiotic<br />
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[[1k6s]] - PaBlac D + phenylboronic acid<br />
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[[1dd6]], [[1h5x]], [[1h8y]], [[2wgv]] - PaBlac D + inhibitor<br />
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[[3isg]] – EcBlac D + inhibitor<br />
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[[3pae]], [[3pag]] - AbBlac D (mutant) + inhibitor<br />
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===AmpC β-lactamase===
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[[1ke4]], [[2bls]], [[2zj9]], [[3bls]] – EcBlac<br />
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[[1l0d]], [[1l0e]], [[1l0f]], [[1l0g]] - EcBlac (mutant)
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[[1fcn ]]– EcBlac (mutant) + substrate<br />
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[[1fco]], [[1i5q]], [[1kvl]] - EcBlac (mutant) + antibiotic<br />
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[[1iel]], [[1fcm]], [[1iem]], [[1kvm]], [[1ll5]], [[1ll9]], [[1llb]] - EcBlac + antibiotic<br />
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[[1fsw]], [[1fsy]], [[1kds]], [[1kdw]], [[1ke0]], [[1ke3]], [[1mxo]], [[1my8]], [[4e3i]], [[4e3j]], [[4e3k]], [[4e3l]], [[4e3m]], [[4e3n]], [[4e3o]] - EcBlac + boronic acid inhibitor<br />
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[[1pi4]], [[1pi5]], [[2ffy]] - EcBlac (mutant) + boronic acid inhibitor<br />
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[[1l2s]], [[1xgi]], [[1xgj]], [[2hdq]], [[2hdr]], [[2hds]], [[2hdu]], [[2p9v]], [[2pu2]], [[2pu4]], [[2r9w]], [[2r9x]], [[2rcx]] - EcBlac + inhibitor<br />
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[[1o07]] - EcBlac (mutant) + inhibitor<br />
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[[3s1y]], [[3s22]] - PaBlac (mutant) + inhibitor<br />
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===Carbapenemase===
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[[3f9o]] - AhBlac B – ''Aeromonas hydrophila''<br />
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[[3fai]], [[1x8h]], [[3sw3]], [[3t9m]] - AhBlac B (mutant)<br />
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[[3rxw]], [[3rxx]] – KpBlac Kpc<br />
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[[2ov5]] - KpBlac A Kpc<br />
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[[4eqi]] – SfBlac Sfc-1<br />
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[[4euz]], [[4ev4]] – SfBlac Sfc-1 (mutant) + antibiotic
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===Extended-spectrum β-lactamase===
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[[3nia]] - PaESBL A GES-2 + inhibitor<br />
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[[3v3s]] – PaESBL GES-18<br />
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[[3v3r]] - AbESBL A GES-11– Acinetobacter baumannii<br />
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[[3tsg]] – AbESBL GES-14<br />
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[[2qpn]] – KpESBL A GES-1<br />
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[[3ni9]] - PaESBL A GES-2
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===Non-classified β-lactamase===
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[[1bsg]] – Blac – ''Streptomyces albus''<br />
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[[1alq]], [[1blp]], [[1dja]], [[1djb]], [[1djc]], [[1ghi]] – SaBlac (mutant) <br />
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[[1gce]], [[1xx2]] - EncBlac <br />
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[[1dy6]] – SmBlac Sme-1<br />
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[[1fr1]], [[1fr6]] – CfBlac <br />
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[[1i2s]] – BlBlac<br />
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[[2gdn]] – MtBlac – ''Mycobacterium tuberculosis''<br />
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[[3vff]], [[3vfh]] – MtBlac (mutant) + intermediate<br />
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[[4df6]] – MtBlac + inhibitor<br />
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[[2jc7]], [[3g4p]] – AbBlac <br />
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[[3byd]] – Blac – ''Klebsiella oxytoca''<br />
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[[3i7j]] – Blac – ''Mycobacterium bovis''<br />
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[[3lez]] – Blac – ''Oceanobacter iheyensis''<br />
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[[3p09]] – Blac – ''Francisella tularensis''<br />
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[[4blm]] - BlBlac
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===Non-classified β-lactamase binary complex===
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[[1ghm]], [[1ghp]], [[1pio]] - SaBlac (mutant) + antibiotic<br />
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[[1blc]], [[1blh]]– SaBlac + inhibitor<br />
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[[1bls ]]– EncBlac + phosphonate derivative <br />
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[[1bul]] - EncBlac + penicillin derivative<br />
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[[1ga0]] - EncBlac + inhibitor<br />
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[[1i2w]] – BlBlac + cifoxitin<br />
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[[3cg5]] – MtBlac + antibiotic<br />
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[[3n8s]], [[3ny4]], [[3n6i]], [[3n7w]], [[3n8l]], [[3n8r]], [[3nbl]], [[3nc8]], [[3nck]], [[3nde]], [[3ndg]] - MtBlac (mutant) + antibiotic<br />
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[[3dwz]], [[3iqa]], [[3m6b]], [[3m6h]] – MtBlac + inhibitor<br />
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[[3fv7]], [[3fyz]], [[3fzc]], [[3mbz]] – AbBlac + inhibitor<br />
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== References ==
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<references/>
[[Category:Topic Page]]
[[Category:Topic Page]]

Current revision

Class B β-lactamase Ndm-1 complex with Zn+2 (grey) (PDB code 3spu)

Drag the structure with the mouse to rotate

References

  1. ↑ Jacoby GA. AmpC beta-lactamases. Clin Microbiol Rev. 2009 Jan;22(1):161-82, Table of Contents. PMID:19136439 doi:10.1128/CMR.00036-08
  2. ↑ King D, Strynadka N. Crystal structure of New Delhi metallo-beta-lactamase reveals molecular basis for antibiotic resistance. Protein Sci. 2011 Sep;20(9):1484-91. doi: 10.1002/pro.697. Epub 2011 Aug, 2. PMID:21774017 doi:10.1002/pro.697

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