penicillin binding proteins
Enable an agent to identify a penicillin-binding protein, assess its supported cell-wall functions and biochemical state, and judge which functional or inhibitor comparisons are justified.
Bundle → Layer → Finding → Questions Filled
6 bundles · 11 layers · 17 findings · 29 questions
PBP identity and family boundaries Resolve which protein is being modeled and why it belongs within this registry concept.
Organism-resolved identity
Anchor the PBP designation to a biological sequence.
Name-to-sequence resolution
Record the organism, locus, accession, allele and sequence version behind each PBP alias.
- Which species, strain, gene locus and protein sequence does this PBP designation identify? definition
- Which curated record or primary experiment establishes the mapping between this alias and that sequence? provenance
Family assignment
Separate PBPs from related or interacting enzymes.
PBP membership evidence
Assess domain architecture, catalytic-site features and functional evidence together, recording the classification scheme used.
- Which sequence, structural or biochemical observations support PBP-family membership and subclass assignment? definition
- What distinguishes this candidate from a beta-lactamase, L,D-transpeptidase or non-PBP glycan polymerase? boundary
Peptidoglycan reaction repertoire Specify the cell-wall reactions attributable to this PBP.
Reaction attribution
Identify the chemical transformation and the domain responsible.
Demonstrated catalytic function
Distinguish measured transpeptidation, carboxypeptidation, endopeptidation and glycan polymerization from inferred annotations.
- Which bonds are formed or cleaved, and which measured products establish that reaction? measurement
- Does the evidence attribute the reaction to this PBP rather than a copurified enzyme or complex partner? boundary
Substrate and kinetic context
Connect catalytic measurements to the tested cell-wall chemistry.
Native substrate relevance
Record substrate structure, reaction conditions and the limits of synthetic substrate surrogates.
- Which stem peptide, cross-bridge, glycan context or lipid-linked substrate was tested, and how does it compare with the organism's peptidoglycan? boundary
- What activity or kinetic parameters were measured at the stated pH, temperature, substrate concentration and membrane conditions? measurement
Cell-envelope integration Locate PBP activity within the organism's cell-wall machinery.
Localization and partner dependence
Record membrane topology, spatial recruitment and required molecular partners.
Productive complex membership
Distinguish association from functional dependence. Reconstituted FtsW polymerase activity required its cognate class B PBP in the reported experiments. [Primary study](https://www.nature.com/articles/s41564-018-0345-x)
- Where is the PBP's catalytic domain located, and what evidence places the protein at septal, lateral or other cell-wall sites? measurement
- Which partners are required for recruitment, activation or productive synthesis, and which merely associate under the tested conditions? boundary
Physiological contribution
Connect PBP activity to growth, morphology and wall composition.
Conditional function and redundancy
Record perturbation and rescue evidence without assuming every PBP is essential or functionally unique.
- Under which strain and growth conditions does loss or inhibition alter viability, morphology or muropeptide composition? measurement
- What complementation or compensating-PBP evidence supports the proposed physiological role? provenance
Beta-lactam engagement and resistance Represent compound-specific target inhibition and its relationship to cellular resistance.
Target engagement
Separate labeling, covalent occupancy and catalytic inhibition.
Compound-specific acylation
Record the compound, active-site modification, kinetic interpretation and any demonstrated regulatory effects. PBP2a studies establish a specific case of ceftaroline-associated allosteric opening; this is not a family-wide assumption. [Primary study](https://pubmed.ncbi.nlm.nih.gov/24085846/)
- Which beta-lactam engages this PBP, with what exposure duration, occupancy and residual catalytic activity? measurement
- Does the reported value describe acylation kinetics, equilibrium binding or a time-dependent competition assay? definition
Resistance attribution
Evaluate what a PBP allele or abundance change explains about susceptibility.
Target change to cellular phenotype
Require evidence connecting the defined PBP change to the observed phenotype while retaining other resistance mechanisms as separate explanations.
- What matched genetic and biochemical evidence connects this PBP variant or expression change to altered drug susceptibility? provenance
- Which effects of beta-lactamase activity, permeability, efflux or other cell-wall changes remain unresolved? boundary
- What resistance inference is justified by these data, and which inference requires additional organism-level testing? action
PBP preparation and assay interpretation Determine whether the tested protein and measurement support the intended conclusion.
Construct and active state
Track experimental departures from the native protein.
Preparation fitness
Record construct boundaries, tags, sequence changes, purity, aggregation and evidence for an active fraction.
- Which native domains, membrane anchors or partner-binding regions are absent or modified in this preparation? boundary
- What measurements establish protein identity, purity and catalytic competence? measurement
- Is this preparation suitable for the proposed catalytic, binding or complex-assembly comparison? action
Readout specificity
Assess whether assay signals uniquely support a PBP-level conclusion.
Orthogonal assay support
Separate band assignment, probe accessibility, product formation and whole-cell effects, preserving negative-result detection limits.
- How was a fluorescent or radiolabeled band assigned to this PBP, and could comigration or probe accessibility explain the signal? provenance
- Which independent product, occupancy or genetic measurement corroborates the interpretation, and what could remain undetected? measurement
Evidence and external alignment What the world already says about this thing, gathered so the model can be checked against it.
Reported evidence
Findings from the breadth pass, kept separate from the structural claims.
Check these first
Recalled without web access and unsourced; every item is a lead to verify.
- Which of these check these first hold for the sense of penicillin binding proteins this model covers, and on what evidence? provenance
Kinds and varieties
Recalled without web access and unsourced; every item is a lead to verify.
- Which of these kinds and varieties hold for the sense of penicillin binding proteins this model covers, and on what evidence? provenance
Identifiers and schemes
Recalled without web access and unsourced; every item is a lead to verify.
- Which of these identifiers and schemes hold for the sense of penicillin binding proteins this model covers, and on what evidence? provenance
Real-world use
Recalled without web access and unsourced; every item is a lead to verify.
- Which of these real-world use hold for the sense of penicillin binding proteins this model covers, and on what evidence? provenance
Typical measurements
Recalled without web access and unsourced; every item is a lead to verify.
- Which of these typical measurements hold for the sense of penicillin binding proteins this model covers, and on what evidence? provenance
Failure modes and hazards
Recalled without web access and unsourced; every item is a lead to verify.
- Which of these failure modes and hazards hold for the sense of penicillin binding proteins this model covers, and on what evidence? provenance
Neighbouring kinds and how to tell them apart
Recalled without web access and unsourced; every item is a lead to verify.
- Which of these neighbouring kinds and how to tell them apart hold for the sense of penicillin binding proteins this model covers, and on what evidence? provenance
Classifiers Filled
- Family
- Thing Registry
- Category
- Physical world and living systems
- Entry kind
- thing
- Plane
- PHY
- Domain
- PHY.MAT
- Other names and narrower kinds
- Penicillin-binding protein, dimerisation domain superfamily, Peptidoglycan D,D-transpeptidase FtsI, Penicillin-binding protein, transpeptidase family, Penicillin-binding protein, dimerisation domain, protein family
What it is Filled
Penicillin-binding proteins (PBPs) are a diverse group of bacterial enzymes involved in peptidoglycan synthesis and remodeling, named for their ability to bind penicillin and related beta-lactam antibiotics through covalent modification of an active-site serine.
In scope
- Species-, strain- and sequence-resolved PBP identities, aliases and variants
- PBP class, domain architecture and catalytic-site integrity
- Peptidoglycan synthesis or remodeling activities and substrate requirements
- Cell-envelope localization, synthesis-complex partners and conditional physiological roles
- Beta-lactam engagement, inhibition and evidence connecting PBP changes to resistance
- Protein preparation, assay conditions and limits of functional attribution
Out of scope
- Penicillin and other antibiotic substances, formulations and dosing
- Whole-organism taxonomy, pathogenicity and complete resistance profiles
- Peptidoglycan as a material and the complete cell-wall biosynthesis pathway
- Beta-lactamases and L,D-transpeptidases as separate enzyme families
- SEDS polymerases and other interacting proteins except their relationships to PBPs
- Clinical treatment selection and patient outcomes
Why it exists Filled
Enable an agent to identify a penicillin-binding protein, assess its supported cell-wall functions and biochemical state, and judge which functional or inhibitor comparisons are justified.
Distinguishing features Filled
- Require a sequence-resolved PBP-family assignment supported by domain, structural or biochemical evidence; a penicillin-labeling signal alone does not establish identity.
- Distinguish peptidoglycan-directed activity from beta-lactam hydrolysis when separating a PBP from a related beta-lactamase.
- Distinguish classical serine-based PBP D,D-peptidase chemistry from L,D-transpeptidase chemistry rather than treating all peptidoglycan cross-linking enzymes as PBPs.
- Assign glycan polymerization to the responsible protein: in the E. coli RodA-PBP2 complex, RodA supplies polymerase activity and PBP2 supplies transpeptidase activity. [Primary structural study](https://www.nature.com/articles/s41467-023-40483-8)
- Resolve numerical names such as PBP2 or PBP5 within an organism; identical numbers across species do not establish equivalent proteins or functions.
What robots and AI may and may not do Filled
Must not
- Treat the presence of a penicillin-binding protein as proof that a bacterium is susceptible to penicillin.
- Infer a patient's appropriate antibiotic treatment from a protein annotation alone.
- Assist in exploiting changes in penicillin-binding proteins to spread harmful antibiotic resistance.
Only with a human decision
- A qualified clinician must decide whether findings involving penicillin-binding proteins justify a treatment change.
May
- Explain the roles of penicillin-binding proteins in bacterial cell wall synthesis and remodeling.
- Summarize documented relationships between these proteins and beta-lactam susceptibility while preserving uncertainty.
Moral aspects Filled
- Overstated susceptibility claims can contribute to ineffective treatment and avoidable patient harm.
- Interpretations of resistance-related findings can influence antibiotic use and its consequences for the wider community.
Who is affected
- Patients receiving treatment for bacterial infections.
- Communities affected by antimicrobial resistance and ineffective antibiotic use.
Owners Filled
Steward
The investigator or clinical specialist responsible for the protein annotation and its interpretation.
Master systems
- Curated protein sequence databases and molecular structure archives.
Links to other meta-models Filled
parent
- Q8054 - registry parent class
What else AI and robots need to interact with it Filled
Identity and identifiers required Filled
- Vercy registry: vr.tr.penicillin-binding-proteins
- Wikidata: Q7162855 (https://www.wikidata.org/wiki/Q7162855)
Direct properties required Filled
- Biological identity: Taxon and strain identifiers; gene locus; protein accession and sequence version
- PBP classification: High-molecular-mass class A; high-molecular-mass class B; low-molecular-mass subclass under a named scheme; unresolved
- Domain and catalytic-site architecture: Domain boundaries, catalytic residues, motif coordinates, membrane anchors and accessory domains
- Molecular mass: kDa; distinguish calculated mature-protein mass from measured apparent mass
- Demonstrated catalytic repertoire: D,D-transpeptidase; D,D-carboxypeptidase; D,D-endopeptidase; glycosyltransferase; other supported activity; unresolved
- Substrate and product specificity: Defined lipid II, stem-peptide, cross-bridge and muropeptide structures with reaction products
- Catalytic performance: kcat in s^-1; Km in µM; catalytic efficiency in M^-1 s^-1; assay-specific alternatives explicitly defined
- Cellular placement and partners: Envelope compartment, septal or lateral distribution, membrane topology and identified interaction partners
- Functional and occupancy state: Active; inactive; unresolved; unmodified; substrate-associated; beta-lactam-acylated; mixed population
- Beta-lactam engagement: Acylation efficiency in M^-1 s^-1; deacylation rate in s^-1; occupancy in %; time-qualified IC50 in µM
- Conditional physiological requirement: Essential; conditionally required; dispensable under tested conditions; unresolved
- Preparation suitability: Native or recombinant; full-length or truncated; purity in % with method; soluble, membrane-reconstituted or aggregated
Recognition required Filled
- A documented structure rendering identifies the protein record and annotates the relevant catalytic domain and active-site serine.
- Different penicillin-binding proteins have different domain arrangements, so no single molecular silhouette establishes identity.
- An image or sample appearance must be linked to supporting molecular characterization to establish a penicillin-binding protein identification.
Capabilities and actions required Filled
- Resolve a PBP name to an organism-specific sequence and classify it with explicit evidence.
- Select substrate and product measurements that discriminate the proposed peptidoglycan reaction.
- Compare inhibitor engagement across defined PBPs while retaining compound, time and assay conditions.
- Relate PBP perturbation to cell-wall composition, morphology and growth under specified conditions.
- Assess whether a construct or purified preparation is suitable for the intended functional comparison.
- Flag unsupported transfers from sequence similarity, protein inhibition or individual variants to organism-level resistance.
Hazards and failure modes required Filled
- Assigning a specific cell-wall function from protein family membership alone can propagate incorrect annotations.
- Assuming that antibiotic binding to an isolated protein guarantees activity against whole bacteria can mislead antimicrobial assessment.
- Treating a protein variant as sufficient evidence of clinical resistance can support inappropriate conclusions about treatment.
Standards and interfaces required Filled
- The Enzyme Commission classification maintained by the International Union of Biochemistry and Molecular Biology includes EC 3.4.16.4 for serine-type D-Ala-D-Ala carboxypeptidase activity found in some penicillin-binding proteins.
Context of use required Filled
- Penicillin-binding proteins are studied in bacterial cell biology to understand peptidoglycan synthesis, remodeling and cell shape.
- They are examined in antimicrobial research to assess enzyme function, antibiotic binding and mechanisms associated with resistance.
Sources Filled
- Wikidata item Q7162855: penicillin binding proteins - identity and sense of the item
- Wikipedia: Penicillin-binding proteins - general description of the item
Open questions
- Which classification scheme best accommodates divergent low-molecular-mass PBPs and atypical homologues without relying on molecular mass or inconsistent class labels?
- What minimum evidence should admit an uncharacterized or weakly penicillin-reactive homologue to this registry concept?
- Which substrate preferences and remodeling activities remain experimentally unresolved for each organism-specific PBP?
- Which localization, partner-dependence and essentiality claims remain valid across strains and environmental conditions?
- For which PBP variants can target-level inhibition measurements explain cellular susceptibility after other resistance mechanisms are accounted for?
Machine files
Provenance
thing registry research (pass 2) · unreviewed
Built from: models/things/publications/thing-q7162855/spec.json