CODSWALLOP

Beta-lactamase TEM

Escherichia coli · seed P62593 · 286 aa · family defined as ≥30% identity to that seed · compiled 07 October 2026

CATH and SCOP identifiers come from the RCSB's own structure annotations, which the Domains panel already reads, so these are looked up rather than guessed at.

769Entries 770Entities 337Constructs 60Organisms 442Ligand-bound
0.79 ÅBest res.
1.65 ÅMedian res.

Every figure here is counted over the whole family rather than quoted from one entry.

The reference structure

1LHY, the structure every other member of this family is superposed onto. Rendered by the RCSB and embedded here: the live app shows an interactive viewport, which a document that fetches nothing cannot.

Rendered structure of 1LHY
1LHY at the RCSB · open it in the 3D viewer

Which residues anyone has ever seen

How many of this family's constructs contain each residue of the seed. A trough is a stretch nobody has put in a construct, which is a construct-design answer rather than a disorder one.

1143286770 constructs

Constructs, most-used first

337 distinct constructs across 769 entries. 655 polymer entities differ from the UniProt canonical sequence in some way, 93 carry a recognised expression tag and 3 carry a fusion partner.

"Differs from canonical" is not the same as "engineered". The canonical sequence is the full gene product, so a secreted protein whose structures all start after its signal peptide counts every one of them as different: lysozyme's most-used construct, residues 19–147 on 1,239 entities, is simply the mature protein. Read the construct column below for what was actually done, rather than this count.

EntitiesLengthBest (Å)Best entryWhat was made
48 263 0.79 4UA6 residues 29-291
27 290 0.98 9F0T His6; Thrombin site; residues 18-293; A18M, F20S, A22S +2 more
25 267 1.72 2GDN residues 41-307
21 265 0.83 8RMA residues 47-311; Y47G, A48P
20 263 0.88 2P74 residues 29-291
18 265 1.05 2ZD8 residues 22-286
15 265 1.40 3N8L residues 43-307; E182A
14 275 1.40 9IVL His6; residues 26-294; H26M, A27G, E170A
11 275 2.00 9UJ6 His6; residues 26-294; H26M, A27G
10 262 0.94 2ZQ7 residues 30-291; E169A, R275N, R277N
10 263 0.85 1M40 residues 24-286; M180T
9 290 1.25 6Z24 His6; Thrombin site; residues 18-293; A18M, F20S, A22S +3 more
8 263 1.73 1JTG residues 24-286; V82I, A182V
8 265 1.30 3M6B residues 43-307
8 291 1.70 9G7V matches the canonical sequence
7 263 1.70 1ERM residues 24-286
7 274 1.19 5NJ2 no UniProt reference for this entity, so it cannot be diffed against a canonical sequence
6 263 1.10 4HBT residues 29-291
6 263 1.45 3HRE residues 29-291; S73G
6 264 1.23 3C5A residues 26-289
6 268 1.44 6B1F residues 22-289
5 261 1.40 7ZPV residues 31-291
5 263 0.85 5VLE residues 29-291; E169A
5 265 1.65 2WK0 residues 43-307; A75T, A147T, V201A +4 more
5 267 1.93 9W7O residues 28-294

Showing the 25 most-used of 337.

Positions people deliberately mutate

Columns where the wild-type residue still dominates but a real minority carries something else, which is a different question from "what varies across species".

E87Q 70% P253A 69% T158F 69% L28A 68% R241T 68% H285E 68% Q37S 67% L282I 67% G85Q 67% T261F 66% A40G 66% V257L 66% D269E 65% R92P 64% L111V 64% T107A 64% I256V 64% N272D 64% I125L 64% V106I 62% C121S 62% I54T 61% E277A 61% W163T 60% T27L 59% L146V 59% S57A 59% I275V 58% R273E 58% V117L 58%

What it assembles into

Oligomeric stateChainsEntriesShare
monomeric1 701 91.2%
dimeric2 55 7.2%
tetrameric4 11 1.4%
trimeric3 2 0.3%

483 entries have the depositor's assembly corroborated by PISA, 270 carry the depositor's word alone and 16 were assigned by PISA where the depositor gave none. The middle figure is not a disagreement: PISA may have returned nothing or never run. 12 entries carry more than one assembly with different chain counts, so they have no single answer to quote: 3LEZ, 4EQI, 4IBR, 4OP5, 4OP8, 4OPQ, 4OPR, 4OPZ, 4OQ0, 4OQH, 4OQI, 6MK6.

Domain architecture

Every source's own domains on the seed axis, one row each. They are not merged: Pfam, CATH, SCOP and InterPro disagree about boundaries, and a merged track would state a consensus none of them gave.

CATHDD-peptidase/beta-lactamasSCOP2Bbeta-lactamase/transpeptidbeta-lactamase/transpeptidbeta-lactamase/transpeptidbeta-lactamase/transpeptidbeta-lactamase/transpeptidbeta-lactamase/transpeptidbeta-lactamase/transpeptidbeta-lactamase/transpeptidbeta-lactamase/transpeptidbeta-lactamase/transpeptidbeta-lactamase/transpeptidbeta-lactamase/transpeptidbeta-lactamase/transpeptidbeta-lactamase/transpeptid1143286
DomainSourceSpan (seed)Chains
DD-peptidase/beta-lactamase superfamilyCATH 3.40.710.10 33–286 581
Periplasmic binding protein-like IICATH 3.40.190.10 281–286 10
beta-lactamase/transpeptidase-likeSCOP2B 8041576 24–286 77
beta-lactamase/transpeptidase-likeSCOP2B 8038399 25–286 43
beta-lactamase/transpeptidase-likeSCOP2B 8069801 31–286 37
beta-lactamase/transpeptidase-likeSCOP2B 8069815 31–286 31
beta-lactamase/transpeptidase-likeSCOP2B 8037342 31–286 16
beta-lactamase/transpeptidase-likeSCOP2B 8069805 32–286 50
beta-lactamase/transpeptidase-likeSCOP2B 8069809 33–286 12
beta-lactamase/transpeptidase-likeSCOP2B 8069821 34–286 18
beta-lactamase/transpeptidase-likeSCOP2B 8069779 34–286 8
beta-lactamase/transpeptidase-likeSCOP2B 8069823 35–286 78

What binds it

MA4 MA440 entries NXL NXL36 entries TSL TSL13 entries YCH YCH12 entries CEF CEF11 entries 9F2 9F211 entries CB4 CB410 entries CAZ CAZ9 entries 4D6 4D69 entries TBE TBE8 entries MK7 MK78 entries IM2 IM27 entries
ComponentClassNameEntriesBest (Å)
SO4ion Sulfate Ion 204 0.83
PO4ion Phosphate Ion 105 0.79
GOLcryoprotectant Glycerol 105 0.98
CLion Chloride Ion 81 0.83
EDOcryoprotectant 1,2-Ethanediol 63 1.08
NAion Sodium Ion 43 0.83
MA4ligand Cyclohexyl-Hexyl-Beta-D-Maltoside 40 0.90
ACTcryoprotectant Acetate Ion 36 1.19
PEGcryoprotectant Di(Hydroxyethyl)ether 36 1.19
NXLligand (2s,5r)-1-Formyl-5-[(Sulfooxy)amino]piperidine-2-Carboxamide 36 0.83
Kion Potassium Ion 23 0.79
EPEbuffer 4-(2-Hydroxyethyl)-1-Piperazine Ethanesulfonic Acid 23 0.90
PG4cryoprotectant Tetraethylene Glycol 20 1.05
BO4ion Borate Ion 20 1.50
DMScryoprotectant Dimethyl Sulfoxide 19 0.85
CITbuffer Citric Acid 18 0.99
CAion Calcium Ion 18 1.05
TSLligand Trans-Enamine Intermediate Of Sulbactam 13 1.30
YCHligand [(4~{S})-2-Oxidanyl-1,3,2-Dioxaborolan-4-Yl]methanol 12 1.00
MESbuffer 2-(N-Morpholino)-Ethanesulfonic Acid 11 1.05

How it crystallises

Parsed from the free text 721 depositors typed into _exptl_crystal_grow.pdbx_details, out of 744 entries that recorded anything at all. Median pH 7.0 (range 3.4 to 9.5).

Precipitants

PEG × Ammonium sulfate × Lithium sulfate × Ethanol × Sodium citrate × Ammonium phosphate × Sodium chloride × Magnesium chloride × Sodium formate × Tacsimate × MPD × Calcium chloride × Isopropanol × Sodium malonate ×

Buffers

Sodium acetate × HEPES × Tris × Phosphate × Citrate × MES × Bis-Tris × Sodium cacodylate × Bis-Tris propane × Imidazole × Glycine × CHES × Succinate ×

Which entries to trust

769 entries carry a wwPDB validation report: 584 clean, 125 worth a check and 60 with something to explain. Median clashscore 3.81, median RSRZ outliers 1.54%, median R-free minus R-work 0.034. 745 have released structure factors.

Across species

OrganismEntriesBest (Å)Ligand-boundSeed covered
Escherichia coli234 0.79 118 100%
Klebsiella pneumoniae225 0.83 163 99%
Mycobacterium tuberculosis66 1.19 40 86%
Bacillus licheniformis32 1.24 19 87%
Serratia marcescens31 1.40 28 89%
Mycobacterium tuberculosis H37Rv20 1.40 16 86%
synthetic construct19 1.30 5 93%
Staphylococcus aureus17 1.76 4 90%
Pseudomonas aeruginosa16 0.96 5 90%
Burkholderia thailandensis9 1.30 4 86%
Klebsiella pneumoniae IS536 0.91 0 89%
Klebsiella pneumoniae subsp. pneumoniae HS112866 1.17 3 89%

Seed sequence

286 residues, numbered every ten. Every identity figure in this document is measured against this sequence.

active or binding site modified residue or glycosylation disulphide cysteine transmembrane or signal the 15 most-substituted positions

1MSIQHFRVAL IPFFAAFCLP VFAHPETLVK VKDAEDQLGA RVGYIELDLN SGKILESFRP
61EERFPMMSTF KVLLCGAVLS RVDAGQEQLG RRIHYSQNDL VEYSPVTEKH LTDGMTVREL
121CSAAITMSDN TAANLLLTTI GGPKELTAFL HNMGDHVTRL DRWEPELNEA IPNDERDTTM
181PAAMATTLRK LLTGELLTLA SRQQLIDWME ADKVAGPLLR SALPAGWFIA DKSGAGERGS
241RGIIAALGPD GKPSRIVVIY TTGSQATMDE RNRQIAEIGA SLIKHW

Sites are UniProt's curated features where the seed is a UniProt accession; the substituted positions are measured from this family's own alignment rather than annotated, and only the fifteen most substituted are marked: every position carrying a minority substitution would be most of the protein, because the family holds orthologues. A residue can carry more than one and is drawn with the first that applies, in the order of the key above.

Primary citations

One record per paper, not per entry.

YearCitation
2026 NCY-1 beta-Lactamase Activity Correlates With Antimicrobial Susceptibility of a Clinical Strain of Nocardia cyriacigeorgica. Microbiologyopen doi:10.1002/mbo3.70267
2026 Fused 3D boron heterocycles via EnT catalysis: synthesis, modification and validation as beta-lactamase inhibitors. Chem Sci doi:10.1039/d5sc05518k
2026 Drop-on-fixed-target reaction initiation approach for serial and time-resolved crystallography. Iucrj doi:10.1107/S2052252526003489
2026 Structure-Based Design of Reversible, Quinoline-2(1 H )‐one Inhibitors of Serine- and Metallo-Carbapenemases. Acs Omega doi:10.1021/acsomega.5c12676
2026 Beyond structure and activity: targeting class A carbapenemases with monocyclic and bicyclic boronic acids to counter antimicrobial resistance. Org.Biomol.Chem. doi:10.1039/d5ob01703c
2026 A novel fusion tool to enable G protein-coupled receptor structure determination. Acta Crystallogr D Struct Biol doi:10.1107/S2059798326003785
2025 Structural genomics of bacterial drug targets: Application of a high-throughput pipeline to solve 58 protein structures from pathogenic and related bacteria. Microbiol Resour Announc doi:10.1128/mra.00200-25
2025 Burkholderia pseudomallei PenI beta-lactamase and variants are potently inhibited by taniborbactam. Antimicrob.Agents Chemother. doi:10.1128/aac.00787-25
2025 Directed evolution of a beta-lactamase samples a wide variety of conformational states. Protein Sci. doi:10.1002/pro.70322
2025 Phosphate ions modulate enzyme activity and epistatic effects in two clavulanic acid-resistant beta-lactamase mutants. Protein Sci. doi:10.1002/pro.70325
2025 Combining MicroED and native mass spectrometry for structural discovery of enzyme-small molecule complexes. Proc.Natl.Acad.Sci.USA doi:10.1073/pnas.2503780122
2025 A beta-lactamase inhibitory protein mutant displays high potency and a broad inhibition profile due to an altered binding mode with beta-lactamases. J.Biol.Chem. doi:10.1016/j.jbc.2025.110850
2025 Probing the modulation of enzyme kinetics by multi-temperature, time-resolved serial crystallography. Nat Commun doi:10.1038/s41467-025-61631-2
2025 Binding mode of Isoxazolyl Penicillins to a Class-A beta-lactamase at ambient conditions. Commun Chem doi:10.1038/s42004-025-01801-x
2025 A glycine at position 105 leads to clavulanic acid and avibactam resistance in class A beta-lactamases. J.Biol.Chem. doi:10.1016/j.jbc.2025.110347
2025 Structural Insights into the Role of the Stereochemistry of the Cyclopropyl Ring in the Inhibitory Activity of Xeruborbactam against SME-1 Class A Carbapenemase. Biochemistry doi:10.1021/acs.biochem.5c00336
2024 Time-resolved crystallography of boric acid binding to the active site serine of the beta-lactamase CTX-M-14 and subsequent 1,2-diol esterification. Commun Chem doi:10.1038/s42004-024-01236-w
2024 Crystal structure of the class A extended-spectrum beta-lactamase CTX-M-96 in complex with relebactam at 1.03 Angstrom resolution. Antimicrob.Agents Chemother. doi:10.1128/aac.01721-23
2024 Dynamical responses predict a distal site that modulates activity in an antibiotic resistance enzyme. Chem Sci doi:10.1039/d4sc03295k
2024 Biochemical and structural characterization of a class A beta-lactamase from Nocardia cyriacigeorgica. Acta Crystallogr.,Sect.F doi:10.1107/S2053230X23010671
2024 Characterization of the extended substrate spectrum of the class A beta-lactamase CESS-1 from Stenotrophomonas sp. and structure-based investigation into its substrate preference. Int J Antimicrob Agents doi:10.1016/j.ijantimicag.2024.107171
2024 Conserved proline residues prevent dimerization and aggregation in the beta-lactamase BlaC. Protein Sci. doi:10.1002/pro.4972
2024 A low-barrier proton shared between two aspartates acts as a conformational switch that changes the substrate specificity of the beta-lactamase BlaC. Int.J.Biol.Macromol. doi:10.1016/j.ijbiomac.2024.134665
2024 Network of epistatic interactions in an enzyme active site revealed by large-scale deep mutational scanning. Proc.Natl.Acad.Sci.USA doi:10.1073/pnas.2313513121
2024 Restricted Rotational Flexibility of the C5 alpha-Methyl-Substituted Carbapenem NA-1-157 Leads to Potent Inhibition of the GES-5 Carbapenemase. Acs Infect Dis. doi:10.1021/acsinfecdis.3c00683
2024 Simultaneous enhancement of multiple functional properties using evolution-informed protein design. Nat Commun doi:10.1038/s41467-024-49119-x
2024 A systematic comparison of Kapton-based HARE chips for fixed-target serial crystallography Cell Rep Phys Sci doi:10.1016/j.xcrp.2024.101987
2023 Biochemical and Structural Characterization of CRH-1, a Carbapenemase from Chromobacterium haemolyticum Related to KPC beta-Lactamases. Antimicrob.Agents Chemother. doi:10.1128/aac.00061-23
2023 Tautomer-Specific Deacylation and Omega-Loop Flexibility Explain the Carbapenem-Hydrolyzing Broad-Spectrum Activity of the KPC-2 beta-Lactamase. J.Am.Chem.Soc. doi:10.1021/jacs.2c12123
2023 Exploring avibactam and relebactam inhibition of Klebsiella pneumoniae carbapenemase D179N variant: role of the Omega loop-held deacylation water. Antimicrob.Agents Chemother. doi:10.1128/aac.00350-23
2023 Klebsiella pneumoniae carbapenemase variant 44 acquires ceftazidime-avibactam resistance by altering the conformation of active-site loops. J.Biol.Chem. doi:10.1016/j.jbc.2023.105493
2023 Mapping the determinants of catalysis and substrate specificity of the antibiotic resistance enzyme CTX-M beta-lactamase. Commun Biol doi:10.1038/s42003-023-04422-z
2023 Mutagenesis and structural analysis reveal the CTX-M beta-lactamase active site is optimized for cephalosporin catalysis and drug resistance. J.Biol.Chem. doi:10.1016/j.jbc.2023.104630
2023 Boronic Acid Transition State Inhibitors as Potent Inactivators of KPC and CTX-M beta-Lactamases: Biochemical and Structural Analyses. Antimicrob.Agents Chemother. doi:10.1128/aac.00930-22
2023 Millisecond cryo-trapping by the spitrobot crystal plunger simplifies time-resolved crystallography. Nat Commun doi:10.1038/s41467-023-37834-w
2023 Asp179 in the class A beta-lactamase from Mycobacterium tuberculosis is a conserved yet not essential residue due to epistasis. Febs J. doi:10.1111/febs.16892
2023 Enhanced activity against a third-generation cephalosporin by destabilization of the active site of a class A beta-lactamase. Int.J.Biol.Macromol. doi:10.1016/j.ijbiomac.2023.126160
2023 Heterogeneity in M. tuberculosis beta-lactamase inhibition by Sulbactam. Nat Commun doi:10.1038/s41467-023-41246-1
2022 Penicillanic Acid Sulfones Inactivate the Extended-Spectrum beta-Lactamase CTX-M-15 through Formation of a Serine-Lysine Cross-Link: an Alternative Mechanism of beta-Lactamase Inhibition. Mbio doi:10.1128/mbio.01793-21
2022 Structural Characterization of the D179N and D179Y Variants of KPC-2 beta-Lactamase: Omega-Loop Destabilization as a Mechanism of Resistance to Ceftazidime-Avibactam. Antimicrob.Agents Chemother. doi:10.1128/aac.02414-21