Lactamase_B

Metallo-beta-lactamase superfamily

• SMART accession number: SM00849
• Description: Apart from the beta-lactamases a number of other proteins contain this domain (PUBMED:7588620). These proteins include thiolesterases, members of the glyoxalase II family, that catalyse the hydrolysis of S-D-lactoyl-glutathione to form glutathione and D-lactic acid and a competence protein that is essential for natural transformation in Neisseria gonorrhoeae and could be a transporter involved in DNA uptake. Except for the competence protein these proteins bind two zinc ions per molecule as cofactor.
• Interpro abstract (IPR001279): Apart from the beta-lactamases and metallo-beta-lactamases, a number of other proteins contain this domain [(PUBMED:7588620)]. These proteins include thiolesterases, members of the glyoxalase II family, that catalyse the hydrolysis of S-D-lactoyl-glutathione to form glutathione and D-lactic acid and a competence protein that is essential for natural transformation in Neisseria gonorrhoeae and could be a transporter involved in DNA uptake. Except for the competence protein these proteins bind two zinc ions per molecule as cofactor.
• GO function: hydrolase activity (GO:0016787)

There are 19064 Lactamase_B domains in 19061 proteins in SMART's nrdb database.

Cellular role (predicted cellular role)

Cellular role: metabolism

Literature (relevant references for this domain)

Primary literature is listed below; Automatically-derived, secondary literature is also avaliable.

• Neuwald AF, Liu JS, Lipman DJ, Lawrence CE
• Extracting protein alignment models from the sequence database.
• Nucleic Acids Res. 1997; 25: 1665-77

Biologists often gain structural and functional insights into a proteinsequence by constructing a multiple alignment model of the family. Here aprogram called Probe fully automates this process of model constructionstarting from a single sequence. Central to this program is a powerful newmethod to locate and align only those, often subtly, conserved patternsessential to the family as a whole. When applied to randomly chosenproteins, Probe found on average about four times as many relationships asa pairwise search and yielded many new discoveries. These include: anobscure subfamily of globins in the roundworm Caenorhabditis elegans ; twonew superfamilies of metallohydrolases; a lipoyl/biotin swinging armdomain in bacterial membrane fusion proteins; and a DH domain in the yeastBud3 and Fus2 proteins. By identifying distant relationships and mergingfamilies into superfamilies in this way, this analysis further confirmsthe notion that proteins evolved from relatively few ancient sequences.Moreover, this method automatically generates models of these ancientconserved regions for rapid and sensitive screening of sequences.

• Carfi A et al.
• The 3-D structure of a zinc metallo-beta-lactamase from Bacillus cereusreveals a new type of protein fold.
• EMBO J. 1995; 14: 4914-21

The 3-D structure of Bacillus cereus (569/H/9) beta-lactamase (EC3.5.2.6), which catalyses the hydrolysis of nearly all beta-lactams, hasbeen solved at 2.5 A resolution by the multiple isomorphous replacementmethod, with density modification and phase combination, from crystals ofthe native protein and of a specially designed mutant (T97C). The currentmodel includes 212 of the 227 amino acid residues, the zinc ion and 10water molecules. The protein is folded into a beta beta sandwich withhelices on each external face. To our knowledge, this fold has never beenobserved. An approximate internal molecular symmetry is found, with a2-fold axis passing roughly through the zinc ion and suggesting a possiblegene duplication. The active site is located at one edge of the beta betasandwich and near the N-terminal end of a helix. The zinc ion iscoordinated by three histidine residues (86, 88 and 149) and a watermolecule. A sequence comparison of the relevant metallo-beta-lactamases,based on this protein structure, highlights a few well-conserved aminoacid residues. The structure shows that most of these residues are in theactive site. Among these, aspartic acid 90 and histidine 210 participatein a proposed catalytic mechanism for beta-lactam hydrolysis.

Metabolism (metabolic pathways involving proteins which contain this domain)

% proteins involved	KEGG pathway ID	Description
50.65	map00620	Pyruvate metabolism
19.30	map03090	Type II secretion system
7.26	map00312	beta-Lactam resistance
7.26	map00311	Penicillin and cephalosporin biosynthesis
7.26	map02020	Two-component system - General
3.05	map00053	Ascorbate and aldarate metabolism
0.73	map00230	Purine metabolism
0.44	map01056	Biosynthesis of type II polyketide backbone
0.44	map04914	Progesterone-mediated oocyte maturation
0.29	map00350	Tyrosine metabolism
0.29	map00930	Caprolactam degradation
0.29	map00903	Limonene and pinene degradation
0.29	map00860	Porphyrin and chlorophyll metabolism
0.29	map00340	Histidine metabolism
0.29	map00632	Benzoate degradation via CoA ligation
0.15	map00260	Glycine, serine and threonine metabolism
0.15	map00785	Lipoic acid metabolism
0.15	map00650	Butanoate metabolism
0.15	map00240	Pyrimidine metabolism
0.15	map00624	1- and 2-Methylnaphthalene degradation
0.15	map02010	ABC transporters - General
0.15	map00120	Bile acid biosynthesis
0.15	map00290	Valine, leucine and isoleucine biosynthesis
0.15	map00150	Androgen and estrogen metabolism
0.15	map00460	Cyanoamino acid metabolism
0.15	map00362	Benzoate degradation via hydroxylation
0.15	map00600	Sphingolipid metabolism
0.15	map00730	Thiamine metabolism

This information is based on mapping of SMART genomic protein database to KEGG orthologous groups. Percentage points are related to the number of proteins with Lactamase_B domain which could be assigned to a KEGG orthologous group, and not all proteins containing Lactamase_B domain. Please note that proteins can be included in multiple pathways, ie. the numbers above will not always add up to 100%.

Structure (3D structures containing this domain)

3D Structures of Lactamase_B domains in PDB

PDB code	Title
1a7t	Metallo-beta-lactamase with mes
1a8t	Metallo-beta-lactamase in complex with l-159,061
1bc2	Zn-dependent metallo-beta-lactamase from bacillus cereus
1bmc	Structure of a zinc metallo-beta-lactamase from bacillus cereus
1bvt	Metallo-beta-lactamase from bacillus cereus 569/h/9
1dd6	Imp-1 metallo beta-lactamase from pseudomonas aeruginosa in complex with a mercaptocarboxylate inhibitor
1ddk	Crystal structure of imp-1 metallo beta-lactamase from pseudomonas aeruginosa
1dxk	Metallo-beta-lactamase from bacillus cereus 569/h/9 c168s mutant
1e5d	Rubredoxin oxygen:oxidoreductase (roo) from anaerobe desulfovibrio gigas
1hlk	Metallo-beta-lactamase from bacteroides fragilis in complex with a tricyclic inhibitor
1jje	Imp-1 metallo beta-lactamase from pseudomonas aeruginosa in complex with a biaryl succinic acid inhibitor (11)
1jjt	Imp-1 metallo beta-lactamase from pseudomonas aeruginosa in complex with a biaryl succinic acid inhibitor (1)
1jt1	Fez-1 metallo-beta-lactamase from legionella gormanii modelled with d-captopril
1k07	Native fez-1 metallo-beta-lactamase from legionella gormanii
1ko2	Vim-2, a zn-beta-lactamase from pseudomonas aeruginosa with an oxidized cys (cysteinesulfonic)
1ko3	Vim-2, a zn-beta-lactamase from pseudomonas aeruginosa with cys221 reduced
1kr3	Crystal structure of the metallo beta-lactamase from bacteroides fragilis (cfia) in complex with the tricyclic inhibitor sb-236050.
1l9y	Fez-1-y228a, a mutant of the metallo-beta-lactamase from legionella gormanii
1m2x	Crystal structure of the metallo-beta-lactamase blab of chryseobacterium meningosepticum in complex with the inhibitor d-captopril
1mqo	Metallo-beta-lactamase bcii cd substituted from bacillus cereus at 1.35 angstroms resolution
1p9e	Crystal structure analysis of methyl parathion hydrolase from pseudomonas sp wbc-3
1qh3	Human glyoxalase ii with cacodylate and acetate ions present in the active site
1qh5	Human glyoxalase ii with s-(n-hydroxy-n- bromophenylcarbamoyl)glutathione
1sml	Metallo beta lactamase l1 from stenotrophomonas maltophilia
1vgn	Structure-based design of the irreversible inhibitors to metallo--lactamase (imp-1)
1vme	Crystal structure of flavoprotein (tm0755) from thermotoga maritima at 1.80 a resolution
1wra	Crystal structure of phosphorylcholine esterase domain of the virulence factor choline binding protein e from streptococcus pneumoniae
1wuo	Crystal structure of metallo-beta-lactamase imp-1 mutant (d81a)
1wup	Crystal structure of metallo-beta-lactamase imp-1 mutant (d81e)
1ww1	Crystal structure of trnase z from thermotoga maritima
1x8g	Crystal structure of the mono-zinc carbapenemase cpha from aeromonas hydrophyla
1x8h	The mono-zinc carbapenemase cpha (n220g mutant) shows a zn(ii)- nh2 arg coordination
1x8i	Crystal structure of the zinc carbapenemase cpha in complex with the antibiotic biapenem
1xm8	X-ray structure of glyoxalase ii from arabidopsis thaliana gene at2g31350
1y44	Crystal structure of rnase z
1ycf	Oxidized (di-ferric) fpra from moorella thermoacetica
1ycg	X-ray structures of moorella thermoacetica fpra. novel diiron site structure and mechanistic insights into a scavenging nitric oxide reductase
1ych	X-ray crystal structures of moorella thermoacetica fpra. novel diiron site structure and mechanistic insights into a scavenging nitric oxide reductase
1zkp	1.5a resolution crystal structure of a metallo beta lactamase family protein, the elac homolgue of bacillus anthracis, a putative ribonuclease
1znb	Metallo-beta-lactamase
1ztc	Crystal structure of a putative metallo-beta-lactamase (tm0894) from thermotoga maritima at 2.10 a resolution
2a7m	1.6 angstrom resolution structure of the quorum-quenching n- acyl homoserine lactone hydrolase of bacillus thuringiensis
2aio	Metallo beta lactamase l1 from stenotrophomonas maltophilia complexed with hydrolyzed moxalactam
2az4	Crystal structure of a protein of unknown function from enterococcus faecalis v583
2bc2	Metallo beta-lactamase ii from bacillus cereus 569/h/9 at ph 6.0, trigonal crystal form
2bfk	Bacillus cereus metallo-beta-lactamase (bcii) arg (121) cys mutant. solved at ph7 using 20mm znso4 in buffer. 1mm dtt was used as a reducing agent
2bfl	Bacillus cereus metallo-beta-lactamase (bcii) arg (121) cys mutant. solved at ph5 using 20mm znso4 in buffer. 1mm dtt was used as a reducing agent.
2bfz	Bacillus cereus metallo-beta-lactamase (bcii) arg (121) cys mutant. solved at ph4.5 using 20mm znso4 in buffer. 1mm dtt was used as a reducing agent. cys221 is oxidized.
2bg2	Bacillus cereus metallo-beta-lactamase (bcii) arg (121) cys mutant. solved at ph4.5 using 20mm znso4 in the buffer. 1mm dtt and 1mm tcep-hcl were used as reducing agents. cys221 is reduced.
2bg6	Bacillus cereus metallo-beta-lactamase (bcii) arg (121) cys mutant. solved at ph5 using 20 micromolar znso4 in the buffer. 1mm dtt was used as a reducing agent. cys221 is oxidized.
2bg7	Bacillus cereus metallo-beta-lactamase (bcii) arg (121) cys mutant. solved at ph4.5 using 20 micromolar znso4 in the buffer. 1mm dtt was used as a reducing agent. cys221 is oxidized.
2bg8	Bacillus cereus metallo-beta-lactamase (bcii) arg (121) cys mutant. solved at ph4.5 using 20 micromolar znso4 in the buffer. 1mm dtt and 1mm tcep-hcl were used as reducing agents.
2bga	Bacillus cereus metallo-beta-lactamase (bcii) arg (121) cys mutant. solved at ph7 using 20 micromolar znso4 in the buffer. 1mm dtt was used as a reducing agent. cys221 is oxidized.
2bib	Crystal structure of the complete modular teichioic acid phosphorylcholine esterase pce (cbpe) from streptococcus pneumoniae
2bmi	Metallo-beta-lactamase
2br6	Crystal structure of quorum-quenching n-acyl homoserine lactone lactonase
2btn	Crystal structure and catalytic mechanism of the quorum- quenching n-acyl homoserine lactone hydrolase
2cbn	Crystal structure of zipd from escherichia coli
2cfu	Crystal structure of sdsa1, an alkylsulfatase from pseudomonas aeruginosa, in complex with 1-decane-sulfonic- acid.
2cfz	Crystal structure of sdsa1, an alkylsulfatase from pseudomonas aeruginosa, in complex with 1-dodecanol
2cg2	Crystal structure of sdsa1, an alkylsulfatase from pseudomonas aeruginosa, in complex with sulfate
2cg3	Crystal structure of sdsa1, an alkylsulfatase from pseudomonas aeruginosa.
2dkf	Crystal structure of ttha0252 from thermus thermophilus hb8, a rna degradation protein of the metallo-beta-lactamase superfamily
2doo	The structure of imp-1 complexed with the detecting reagent (dansylc4sh) by a fluorescent probe
2e7y	High resolution structure of t. maritima trnase z
2fhx	Pseudomonas aeruginosa spm-1 metallo-beta-lactamase
2fk6	Crystal structure of rnase z/trna(thr) complex
2fm6	Zinc-beta-lactamase l1 from stenotrophomonas maltophilia (native form)
2fu6	Zinc-beta-lactamase l1 from stenotrophomonas maltophilia (apo form)
2fu7	Zinc-beta-lactamase l1 from stenotrophomonas maltophilia (cu-substituted form)
2fu8	Zinc-beta-lactamase l1 from stenotrophomonas maltophilia (d- captopril complex)
2fu9	Zinc-beta-lactamase l1 from stenotrophomonas maltophilia (mp2 inhibitor complex)
2gcu	X-ray structure of gene product from arabidopsis thaliana at1g53580
2gfj	Crystal structure of the zinc-beta-lactamase l1 from stenotrophomonas maltophilia (inhibitor 1)
2gfk	Crystal structure of the zinc-beta-lactamase l1 from stenotrophomonas maltophilia (inhibitor 2)
2gkl	Crystal structure of the zinc carbapenemase cpha in complex with the inhibitor pyridine-2,4-dicarboxylate
2gmn	Crystal structure of bjp-1, a subclass b3 metallo-beta- lactamase of bradyrhizobium japonicum
2h6a	Crystal structure of the zinc-beta-lactamase l1 from stenotrophomonas maltophilia (mono zinc form)
2hb9	Crystal structure of the zinc-beta-lactamase l1 from stenotrophomonas maltophilia (inhibitor 3)
2i7t	Structure of human cpsf-73
2i7v	Structure of human cpsf-73
2nxa	Structure of zn-dependent metallo-beta-lactamase from bacillus cereus r121h, c221d double mutant
2nyp	Structure of beta-lactamase ii from bacillus cereus. r121h, c221d doble mutant with two zinc ions.
2nze	Structure of beta-lactamase ii from bacillus cereus. r121h, c221s double mutant. space group p3121.
2nzf	Structure of beta-lactamase ii from bacillus cereus. r121h, c221s double mutant. space group c2.
2ohh	Crystal structure of coenzyme f420h2 oxidase (fpra), a diiron flavoprotein, active oxidized state
2ohi	Crystal structure of coenzyme f420h2 oxidase (fpra), a diiron flavoprotein, reduced state
2ohj	Crystal structure of coenzyme f420h2 oxidase (fpra), a diiron flavoprotein, inactive oxidized state
2p18	Crystal structure of the leishmania infantum glyoxalase ii
2p1e	Crystal structure of the leishmania infantum glyoxalase ii with d-lactate at the active site
2p4z	A ferredoxin-like metallo-beta-lactamase superfamily protein from thermoanaerobacter tengcongensis
2p97	Crystal structure of hypothetical protein (yp_323572.1) from anabaena variabilis atcc 29413 at 1.65 a resolution
2q0i	Structure of pseudomonas quinolone signal response protein pqse
2q0j	Structure of pseudomonas quinolone signal response protein pqse
2q42	Ensemble refinement of the protein crystal structure of glyoxalase ii from arabidopsis thaliana gene at2g31350
2q9u	Crystal structure of the flavodiiron protein from giardia intestinalis
2qds	Crystal structure of the zinc carbapenemase cpha in complex with the inhibitor d-captopril
2qdt	Structural basis for the broad-spectrum inhibition of metallo-{beta}-lactamases: l1- is38 complex
2qed	Crystal structure of salmonella thyphimurium lt2 glyoxalase ii
2qin	Stenotrophomonas maltophilia l1 metallo-beta-lactamase asp- cys mutant
2qjs	Stenotrophomonas maltophilia l1 metallo-beta-lactamase asp- asn mutant
2r2d	Structure of a quorum-quenching lactonase (aiib) from agrobacterium tumefaciens
2uyx	Metallo-beta-lactamase (1bc2) single point mutant d120s
2yz3	Crystallographic investigation of inhibition mode of the vim-2 metallo-beta-lactamase from pseudomonas aeruginosa with mercaptocarboxylate inhibitor
2znb	Metallo-beta-lactamase (cadmium-bound form)
2zo4	Crystal structure of metallo-beta-lactamase family protein ttha1429 from thermus thermophilus hb8
2zwr	Crystal structure of ttha1623 from thermus thermophilus hb8
3a4y	Crystal structure of h61a mutant ttha0252 from thermus thermophilus hb8
3bc2	Metallo beta-lactamase ii from bacillus cereus 569/h/9 at ph 6.0, monoclinic crystal form
3bk1	Crystal structure analysis of rnase j
3bk2	Crystal structure analysis of the rnase j/ump complex
3bv6	Crystal structure of uncharacterized metallo protein from vibrio cholerae with beta-lactamase like fold
3dh8	Structure of pseudomonas quinolone signal response protein pqse
3dha	An ultral high resolution structure of n-acyl homoserine lactone hydrolase with the product n-hexanoyl-l-homoserine bound at an alternative site
3dhb	1.4 angstrom structure of n-acyl homoserine lactone hydrolase with the product n-hexanoyl-l-homoserine bound at the catalytic metal center
3dhc	1.3 angstrom structure of n-acyl homoserine lactone hydrolase with the product n-hexanoyl-l-homocysteine bound to the catalytic metal center
3esh	Crystal structure of a probable metal-dependent hydrolase from staphylococcus aureus. northeast structural genomics target zr314
3f9o	Crystal structure of the di-zinc carbapenemase cpha from aeromonas hydrophila
3fai	The di zinc carbapenemase cpha n220g mutant
3fcz	Adaptive protein evolution grants organismal fitness by improving catalysis and flexibility
3g1p	Crystals structure of phnp from e.coli k-12
3h3e	Crystal structure of tm1679, a metal-dependent hydrolase of the beta-lactamase superfamily
3hnn	Crystal structure of putative diflavin flavoprotein a 5 (fragment 1-254) from nostoc sp. pcc 7120, northeast structural genomics consortium target nsr435a
3idz	Crystal structure of s378q mutant ttha0252 from thermus thermophilus hb8
3ie0	Crystal structure of s378y mutant ttha0252 from thermus thermophilus hb8
3ie1	Crystal structure of h380a mutant ttha0252 from thermus thermophilus hb8 complexed with rna
3ie2	Crystal structure of h400v mutant ttha0252 from thermus thermophilus hb8
3znb	Metallo-beta-lactamase (zn, hg-bound form)
4znb	Metallo-beta-lactamase (c181s mutant)

Links (links to other resources describing this domain)

• PFAM: Lactamase_B
• INTERPRO: IPR001279