{ "vercy": "1.0-draft", "publication": { "status": "research-draft", "adjudicationStatus": "unreviewed", "publishableCanonical": false, "generatedAt": "2026-09-12T11:58:50Z", "providers": [ "Codex" ], "breadth": "recalled by Codex without web access - no source was read", "missingProviders": [], "pass": 2, "cost": { "grok": { "seconds": 23.2, "error": "Reading additional input from stdin...\nOpenAI Codex v0.153.4\n--------\nworkdir: R:\\02_PROJECTS\\02_Meta_Models_Platforms\\Ver.cy\\current\\thing-registry-backlog\nmodel: gpt-6-astra\nprovider: openai\napproval: never\nsandbox: read-only\nreasoning effort: none\nreasoning summaries: none\nsession id: 01a0957a-c555-73c3-b5f9-9843f84e835f\n--------\nuser\nDescribe what is already known about one registered thing. Answer as JSON only, no prose around it.\n\nThing: penicillin binding proteins\nSense to describe: (none recorded)\nDomain code: PHY.MAT\nAlso known as: (none)\n\n\nContext for this batch of 1001 things:\n# Bat", "usd": 0.0, "recall": true }, "codex": { "seconds": 84.0, "error": "Reading additional input from stdin...\nOpenAI Codex v0.153.4\n--------\nworkdir: R:\\02_PROJECTS\\02_Meta_Models_Platforms\\Ver.cy\\current\\thing-registry-backlog\nmodel: gpt-6-astra\nprovider: openai\napproval: never\nsandbox: read-only\nreasoning effort: none\nreasoning summaries: none\nsession id: 01a0957a-c54b-7822-b316-8bbbbfdde359\n--------\nuser\nYou are drafting a Vercy meta-model for one registered thing. Answer as JSON only, no prose around it.\n\nThing: penicillin binding proteins\nRegistry id: vr.tr.penicillin-binding-proteins\nPlane / domain: PHY / PHY.MAT\nRegistry definition: (none recorded)\nNames f" } }, "enrichment": { "pass": 3, "engine": "codex", "producedAt": "2026-10-08T12:00:00Z", "ingestedAt": "2026-10-08T18:55:14+00:00", "fields": [ "agent_conduct", "ethics", "owners", "visual_identification" ] }, "gate": { "passed": true, "version": "1.0", "at": "2026-10-08T18:56:50+00:00", "evidence": [ "completeness 1.00", "sense: Wikidata description", "2 live sources", "review by codex: pass" ] } }, "metaModel": { "id": "THING-Q7162855", "registryId": "vr.tr.penicillin-binding-proteins", "name": "penicillin binding proteins", "version": "0.1.0-research.1", "entryKind": "thing", "family": "Thing Registry", "domain": [ "PHY.MAT" ], "status": "research-draft" }, "canonicalUrl": "https://ver.cy/models/thing/q7162855/", "model": { "registry_id": "vr.tr.penicillin-binding-proteins", "name": "penicillin binding proteins", "purpose": "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.", "definition": "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.", "scope_statement": "This model owns the protein-family concept registered as vr.tr.penicillin-binding-proteins in PHY / PHY.MAT and the organism-specific identities, catalytic activities, cellular relationships and experimental states of its members; individual proteins and preparations instantiate the model rather than defining a single uniform substance.", "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" ], "distinguishing_features": [ "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." ], "characteristics": [ { "name": "Biological identity", "kind": "relation", "unit_or_values": "Taxon and strain identifiers; gene locus; protein accession and sequence version", "why_it_matters": "Prevents unrelated numbered PBPs or different alleles from being merged." }, { "name": "PBP classification", "kind": "category", "unit_or_values": "High-molecular-mass class A; high-molecular-mass class B; low-molecular-mass subclass under a named scheme; unresolved", "why_it_matters": "Organizes expected architecture without substituting class labels for demonstrated activity." }, { "name": "Domain and catalytic-site architecture", "kind": "category", "unit_or_values": "Domain boundaries, catalytic residues, motif coordinates, membrane anchors and accessory domains", "why_it_matters": "Supports family assignment and identifies truncations or substitutions that affect interpretation." }, { "name": "Molecular mass", "kind": "measurement", "unit_or_values": "kDa; distinguish calculated mature-protein mass from measured apparent mass", "why_it_matters": "Helps interpret protein bands and constructs without making mass alone determine class." }, { "name": "Demonstrated catalytic repertoire", "kind": "category", "unit_or_values": "D,D-transpeptidase; D,D-carboxypeptidase; D,D-endopeptidase; glycosyltransferase; other supported activity; unresolved", "why_it_matters": "Separates cross-link formation, peptide cleavage and glycan polymerization." }, { "name": "Substrate and product specificity", "kind": "relation", "unit_or_values": "Defined lipid II, stem-peptide, cross-bridge and muropeptide structures with reaction products", "why_it_matters": "Determines whether an assay represents the protein's native cell-wall chemistry." }, { "name": "Catalytic performance", "kind": "measurement", "unit_or_values": "kcat in s^-1; Km in µM; catalytic efficiency in M^-1 s^-1; assay-specific alternatives explicitly defined", "why_it_matters": "Permits comparisons only when substrate, construct and reaction conditions are compatible." }, { "name": "Cellular placement and partners", "kind": "relation", "unit_or_values": "Envelope compartment, septal or lateral distribution, membrane topology and identified interaction partners", "why_it_matters": "Connects biochemical activity to the cell-wall process in which it operates." }, { "name": "Functional and occupancy state", "kind": "state", "unit_or_values": "Active; inactive; unresolved; unmodified; substrate-associated; beta-lactam-acylated; mixed population", "why_it_matters": "Distinguishes protein presence from catalytic availability." }, { "name": "Beta-lactam engagement", "kind": "measurement", "unit_or_values": "Acylation efficiency in M^-1 s^-1; deacylation rate in s^-1; occupancy in %; time-qualified IC50 in µM", "why_it_matters": "Captures covalent inhibition without misreporting all binding measurements as equilibrium affinity." }, { "name": "Conditional physiological requirement", "kind": "state", "unit_or_values": "Essential; conditionally required; dispensable under tested conditions; unresolved", "why_it_matters": "Keeps essentiality tied to strain, growth conditions and compensating proteins." }, { "name": "Preparation suitability", "kind": "state", "unit_or_values": "Native or recombinant; full-length or truncated; purity in % with method; soluble, membrane-reconstituted or aggregated", "why_it_matters": "Determines which conclusions a preparation can support." } ], "affordances": [ "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." ], "what_it_is_for": [ "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." ], "standards_and_regulation": [ "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." ], "failure_modes_and_hazards": [ "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." ], "facets_not_applicable": { "recognition": "Penicillin-binding proteins have no reliable visual identifying cues and require molecular or biochemical evidence to distinguish them from other proteins." }, "agent_conduct": { "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." ], "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." ], "requires_human": [ "A qualified clinician must decide whether findings involving penicillin-binding proteins justify a treatment change." ] }, "ethics": { "considerations": [ "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." ], "affected_parties": [ "Patients receiving treatment for bacterial infections.", "Communities affected by antimicrobial resistance and ineffective antibiotic use." ] }, "owners": { "steward": "The investigator or clinical specialist responsible for the protein annotation and its interpretation.", "master_systems": [ "Curated protein sequence databases and molecular structure archives." ] }, "visual_identification": [ "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." ] }, "sources": [ { "id": "wikidata", "title": "Wikidata item Q7162855: penicillin binding proteins", "url": "https://www.wikidata.org/wiki/Q7162855", "url_status": "live", "what_it_supports": "identity and sense of the item", "checked_by": "wikidata-api" }, { "id": "wikipedia-en", "title": "Wikipedia: Penicillin-binding proteins", "url": "https://en.wikipedia.org/wiki/Penicillin-binding_proteins", "url_status": "live", "what_it_supports": "general description of the item", "checked_by": "wikidata-api sitelink" } ], "structure": { "bundles": [ { "id": "pbp-identity-and-family-boundaries", "name": "PBP identity and family boundaries", "description": "Resolve which protein is being modeled and why it belongs within this registry concept.", "rationale": "PBP numbering, homologous catalytic folds and organism-specific repertoires make names insufficient identifiers.", "layers": [ { "id": "organism-resolved-identity", "name": "Organism-resolved identity", "description": "Anchor the PBP designation to a biological sequence.", "findings": [ { "id": "name-to-sequence-resolution", "name": "Name-to-sequence resolution", "description": "Record the organism, locus, accession, allele and sequence version behind each PBP alias.", "questions": [ { "text": "Which species, strain, gene locus and protein sequence does this PBP designation identify?", "kind": "definition", "id": "name-to-sequence-resolution-q01" }, { "text": "Which curated record or primary experiment establishes the mapping between this alias and that sequence?", "kind": "provenance", "id": "name-to-sequence-resolution-q02" } ] } ] }, { "id": "family-assignment", "name": "Family assignment", "description": "Separate PBPs from related or interacting enzymes.", "findings": [ { "id": "pbp-membership-evidence", "name": "PBP membership evidence", "description": "Assess domain architecture, catalytic-site features and functional evidence together, recording the classification scheme used.", "questions": [ { "text": "Which sequence, structural or biochemical observations support PBP-family membership and subclass assignment?", "kind": "definition", "id": "pbp-membership-evidence-q01" }, { "text": "What distinguishes this candidate from a beta-lactamase, L,D-transpeptidase or non-PBP glycan polymerase?", "kind": "boundary", "id": "pbp-membership-evidence-q02" } ] } ] } ] }, { "id": "peptidoglycan-reaction-repertoire", "name": "Peptidoglycan reaction repertoire", "description": "Specify the cell-wall reactions attributable to this PBP.", "rationale": "The family includes different catalytic repertoires; a general cell-wall annotation does not identify the reaction.", "layers": [ { "id": "reaction-attribution", "name": "Reaction attribution", "description": "Identify the chemical transformation and the domain responsible.", "findings": [ { "id": "demonstrated-catalytic-function", "name": "Demonstrated catalytic function", "description": "Distinguish measured transpeptidation, carboxypeptidation, endopeptidation and glycan polymerization from inferred annotations.", "questions": [ { "text": "Which bonds are formed or cleaved, and which measured products establish that reaction?", "kind": "measurement", "id": "demonstrated-catalytic-function-q01" }, { "text": "Does the evidence attribute the reaction to this PBP rather than a copurified enzyme or complex partner?", "kind": "boundary", "id": "demonstrated-catalytic-function-q02" } ] } ] }, { "id": "substrate-and-kinetic-context", "name": "Substrate and kinetic context", "description": "Connect catalytic measurements to the tested cell-wall chemistry.", "findings": [ { "id": "native-substrate-relevance", "name": "Native substrate relevance", "description": "Record substrate structure, reaction conditions and the limits of synthetic substrate surrogates.", "questions": [ { "text": "Which stem peptide, cross-bridge, glycan context or lipid-linked substrate was tested, and how does it compare with the organism's peptidoglycan?", "kind": "boundary", "id": "native-substrate-relevance-q01" }, { "text": "What activity or kinetic parameters were measured at the stated pH, temperature, substrate concentration and membrane conditions?", "kind": "measurement", "id": "native-substrate-relevance-q02" } ] } ] } ] }, { "id": "cell-envelope-integration", "name": "Cell-envelope integration", "description": "Locate PBP activity within the organism's cell-wall machinery.", "rationale": "Localization, partners and functional redundancy determine what an isolated catalytic capability means in a cell.", "layers": [ { "id": "localization-and-partner-dependence", "name": "Localization and partner dependence", "description": "Record membrane topology, spatial recruitment and required molecular partners.", "findings": [ { "id": "productive-complex-membership", "name": "Productive complex membership", "description": "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)", "questions": [ { "text": "Where is the PBP's catalytic domain located, and what evidence places the protein at septal, lateral or other cell-wall sites?", "kind": "measurement", "id": "productive-complex-membership-q01" }, { "text": "Which partners are required for recruitment, activation or productive synthesis, and which merely associate under the tested conditions?", "kind": "boundary", "id": "productive-complex-membership-q02" } ] } ] }, { "id": "physiological-contribution", "name": "Physiological contribution", "description": "Connect PBP activity to growth, morphology and wall composition.", "findings": [ { "id": "conditional-function-and-redundancy", "name": "Conditional function and redundancy", "description": "Record perturbation and rescue evidence without assuming every PBP is essential or functionally unique.", "questions": [ { "text": "Under which strain and growth conditions does loss or inhibition alter viability, morphology or muropeptide composition?", "kind": "measurement", "id": "conditional-function-and-redundancy-q01" }, { "text": "What complementation or compensating-PBP evidence supports the proposed physiological role?", "kind": "provenance", "id": "conditional-function-and-redundancy-q02" } ] } ] } ] }, { "id": "beta-lactam-engagement-and-resistance", "name": "Beta-lactam engagement and resistance", "description": "Represent compound-specific target inhibition and its relationship to cellular resistance.", "rationale": "PBP engagement is time- and compound-dependent, while organism susceptibility also depends on processes outside the target protein.", "layers": [ { "id": "target-engagement", "name": "Target engagement", "description": "Separate labeling, covalent occupancy and catalytic inhibition.", "findings": [ { "id": "compound-specific-acylation", "name": "Compound-specific acylation", "description": "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/)", "questions": [ { "text": "Which beta-lactam engages this PBP, with what exposure duration, occupancy and residual catalytic activity?", "kind": "measurement", "id": "compound-specific-acylation-q01" }, { "text": "Does the reported value describe acylation kinetics, equilibrium binding or a time-dependent competition assay?", "kind": "definition", "id": "compound-specific-acylation-q02" } ] } ] }, { "id": "resistance-attribution", "name": "Resistance attribution", "description": "Evaluate what a PBP allele or abundance change explains about susceptibility.", "findings": [ { "id": "target-change-to-cellular-phenotype", "name": "Target change to cellular phenotype", "description": "Require evidence connecting the defined PBP change to the observed phenotype while retaining other resistance mechanisms as separate explanations.", "questions": [ { "text": "What matched genetic and biochemical evidence connects this PBP variant or expression change to altered drug susceptibility?", "kind": "provenance", "id": "target-change-to-cellular-phenotype-q01" }, { "text": "Which effects of beta-lactamase activity, permeability, efflux or other cell-wall changes remain unresolved?", "kind": "boundary", "id": "target-change-to-cellular-phenotype-q02" }, { "text": "What resistance inference is justified by these data, and which inference requires additional organism-level testing?", "kind": "action", "id": "target-change-to-cellular-phenotype-q03" } ] } ] } ] }, { "id": "pbp-preparation-and-assay-interpretation", "name": "PBP preparation and assay interpretation", "description": "Determine whether the tested protein and measurement support the intended conclusion.", "rationale": "Truncation, membrane removal, inactive protein and overlapping labeling signals can change the meaning of PBP experiments.", "layers": [ { "id": "construct-and-active-state", "name": "Construct and active state", "description": "Track experimental departures from the native protein.", "findings": [ { "id": "preparation-fitness", "name": "Preparation fitness", "description": "Record construct boundaries, tags, sequence changes, purity, aggregation and evidence for an active fraction.", "questions": [ { "text": "Which native domains, membrane anchors or partner-binding regions are absent or modified in this preparation?", "kind": "boundary", "id": "preparation-fitness-q01" }, { "text": "What measurements establish protein identity, purity and catalytic competence?", "kind": "measurement", "id": "preparation-fitness-q02" }, { "text": "Is this preparation suitable for the proposed catalytic, binding or complex-assembly comparison?", "kind": "action", "id": "preparation-fitness-q03" } ] } ] }, { "id": "readout-specificity", "name": "Readout specificity", "description": "Assess whether assay signals uniquely support a PBP-level conclusion.", "findings": [ { "id": "orthogonal-assay-support", "name": "Orthogonal assay support", "description": "Separate band assignment, probe accessibility, product formation and whole-cell effects, preserving negative-result detection limits.", "questions": [ { "text": "How was a fluorescent or radiolabeled band assigned to this PBP, and could comigration or probe accessibility explain the signal?", "kind": "provenance", "id": "orthogonal-assay-support-q01" }, { "text": "Which independent product, occupancy or genetic measurement corroborates the interpretation, and what could remain undetected?", "kind": "measurement", "id": "orthogonal-assay-support-q02" } ] } ] } ] }, { "id": "evidence-and-external-alignment", "name": "Evidence and external alignment", "description": "What the world already says about this thing, gathered so the model can be checked against it.", "rationale": "A model that cannot be lined up against existing standards, identifiers and practice cannot be adopted by anyone who already uses them.", "layers": [ { "id": "reported-evidence", "name": "Reported evidence", "description": "Findings from the breadth pass, kept separate from the structural claims.", "findings": [ { "id": "evidence-confidence-notes", "name": "Check these first", "description": "Recalled without web access and unsourced; every item is a lead to verify.", "evidence": [ "This is a protein group, not a single chemical substance with one formula, purity specification or set of physical constants.", "Classification, molecular mass, essentiality and antibiotic affinity should be checked for the specific organism and protein; not every PBP has every activity listed.", "This account is recalled knowledge without source verification; no regulatory standard or universal substance identifier is asserted." ], "questions": [ { "id": "evidence-confidence-notes-q01", "text": "Which of these check these first hold for the sense of penicillin binding proteins this model covers, and on what evidence?", "kind": "provenance" } ] }, { "id": "evidence-kinds", "name": "Kinds and varieties", "description": "Recalled without web access and unsourced; every item is a lead to verify.", "evidence": [ "Class A high-molecular-mass PBPs with glycosyltransferase and transpeptidase activities", "Class B high-molecular-mass PBPs with transpeptidase activity", "Low-molecular-mass PBPs with DD-carboxypeptidase activity", "Low-molecular-mass PBPs with DD-endopeptidase activity" ], "questions": [ { "id": "evidence-kinds-q01", "text": "Which of these kinds and varieties hold for the sense of penicillin binding proteins this model covers, and on what evidence?", "kind": "provenance" } ] }, { "id": "evidence-identifiers", "name": "Identifiers and schemes", "description": "Recalled without web access and unsourced; every item is a lead to verify.", "evidence": [ { "scheme": "UniProtKB accession", "value_or_pattern": "A six- or ten-character alphanumeric accession for an individual protein entry", "note": "Identifies a particular protein entry rather than the entire PBP group; organism and strain context matter." }, { "scheme": "Organism-specific protein and gene nomenclature", "value_or_pattern": "Protein labels such as PBP1A, PBP2 or PBP3; gene names such as mrcA, mrdA or ftsI in Escherichia coli", "note": "PBP numbering is species-dependent and does not establish equivalent function across organisms." } ], "questions": [ { "id": "evidence-identifiers-q01", "text": "Which of these identifiers and schemes hold for the sense of penicillin binding proteins this model covers, and on what evidence?", "kind": "provenance" } ] }, { "id": "evidence-real-world-use", "name": "Real-world use", "description": "Recalled without web access and unsourced; every item is a lead to verify.", "evidence": [ "Targets of beta-lactam antibiotics that inhibit bacterial cell-wall assembly", "Research into bacterial growth, cell shape, division and peptidoglycan remodeling", "Investigation of antibiotic resistance caused by altered or acquired PBPs", "Biochemical binding and inhibition assays used in antibiotic discovery" ], "questions": [ { "id": "evidence-real-world-use-q01", "text": "Which of these real-world use hold for the sense of penicillin binding proteins this model covers, and on what evidence?", "kind": "provenance" } ] }, { "id": "evidence-measurements", "name": "Typical measurements", "description": "Recalled without web access and unsourced; every item is a lead to verify.", "evidence": [ { "quantity": "Apparent molecular mass", "typical_range": "Approximately 20-50 for many low-molecular-mass PBPs and 50-100 for many high-molecular-mass PBPs; exceptions occur", "unit": "kDa" } ], "questions": [ { "id": "evidence-measurements-q01", "text": "Which of these typical measurements hold for the sense of penicillin binding proteins this model covers, and on what evidence?", "kind": "provenance" } ] }, { "id": "evidence-failure-modes-and-hazards", "name": "Failure modes and hazards", "description": "Recalled without web access and unsourced; every item is a lead to verify.", "evidence": [ "Inhibition of essential PBPs can impair peptidoglycan cross-linking, cause abnormal morphology and lead to bacterial lysis.", "Acquired low-affinity PBPs, including PBP2a associated with mecA in Staphylococcus aureus, can confer resistance to many beta-lactams.", "Mutations or recombination affecting native PBPs can reduce antibiotic susceptibility.", "Binding to an isolated PBP does not by itself demonstrate antibacterial effectiveness; permeability, efflux, beta-lactamase activity and target essentiality also matter.", "Species-dependent numbering can cause incorrect assignments of PBP function or antibiotic specificity." ], "questions": [ { "id": "evidence-failure-modes-and-hazards-q01", "text": "Which of these failure modes and hazards hold for the sense of penicillin binding proteins this model covers, and on what evidence?", "kind": "provenance" } ] }, { "id": "evidence-neighbours", "name": "Neighbouring kinds and how to tell them apart", "description": "Recalled without web access and unsourced; every item is a lead to verify.", "evidence": [ { "name": "Beta-lactamases", "difference": "Beta-lactamases catalytically hydrolyze beta-lactam antibiotics; classical PBPs principally act on peptidoglycan substrates and are inhibited by beta-lactam acylation." }, { "name": "Peptidoglycan", "difference": "Peptidoglycan is the cell-wall polymer that PBPs help synthesize or remodel, rather than an enzyme." }, { "name": "L,D-transpeptidases", "difference": "These enzymes form different peptidoglycan cross-links and generally use a catalytic cysteine, unlike the active-site serine of classical PBPs." }, { "name": "Penicillin", "difference": "Penicillin is a beta-lactam antibiotic ligand and inhibitor of susceptible PBPs, rather than the protein target." } ], "questions": [ { "id": "evidence-neighbours-q01", "text": "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?", "kind": "provenance" } ] } ] } ] } ] }, "openQuestions": [ "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?" ], "statistics": { "bundles": 6, "layers": 11, "findings": 17, "questions": 29 } }