ftsI

UniProt ID: P0AD68
Organism: Escherichia coli (strain K12)
Review Status: COMPLETE
Aliases:
PBP3 PbpB b0084 JW0082
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Gene Description

FtsI (also known as PBP3/PbpB) is an essential peptidoglycan D,D-transpeptidase required for cell division in E. coli. It is a Class B high-molecular-mass penicillin-binding protein that catalyzes cross-linking of peptidoglycan at the division septum. FtsI is a monofunctional transpeptidase - unlike Class A PBPs, it lacks glycosyltransferase activity. FtsI forms a subcomplex with FtsW (a SEDS protein that provides glycosyltransferase activity) and interacts with multiple divisome proteins including FtsQ, FtsL, FtsN, and PBP1b. FtsI localizes to the division septum during later stages of cell growth and throughout septation. Inhibition by beta-lactam antibiotics like penicillin blocks cell division causing filamentation.

Existing Annotations Review

GO Term Evidence Action Reason
GO:0005886 plasma membrane
IBA
GO_REF:0000033
ACCEPT
Summary: FtsI is an integral membrane protein with a single transmembrane helix that anchors it to the plasma membrane. The bulk of the protein protrudes into the periplasmic space [PMID:2677607]. UniProt confirms "Cell inner membrane; Single-pass membrane protein; Periplasmic side."
Reason: Well-supported by phylogenetic inference (IBA) and consistent with the experimentally determined topology of FtsI. The protein contains an N-terminal transmembrane anchor and the periplasmic catalytic domain [PMID:2677607, PMID:9614966].
Supporting Evidence:
file:ECOLI/ftsI/ftsI-deep-research-falcon.md
See deep research file for comprehensive analysis
GO:0008658 penicillin binding
IBA
GO_REF:0000033
ACCEPT
Summary: FtsI (PBP3) is one of the major penicillin-binding proteins in E. coli. Spratt 1975 [PMID:1103132] showed that beta-lactams that specifically inhibit cell division bind preferentially to penicillin binding protein 3.
Reason: Core function of FtsI. Penicillin binding is essential for the mechanism of action of beta-lactam antibiotics against FtsI. Experimentally demonstrated by IDA [PMID:1103132] and confirmed by IBA phylogenetic inference.
Supporting Evidence:
PMID:1103132
beta-Lactams that specifically inhibit cell division bind preferentially to penicillin binding protein 3 (molecular weight 60,000)
GO:0071555 cell wall organization
IBA
GO_REF:0000033
ACCEPT
Summary: FtsI participates in peptidoglycan synthesis at the division septum, contributing to cell wall organization during cell division. Botta and Park [PMID:6450748] showed PBP3 activity is required for septal murein synthesis.
Reason: Appropriate biological process annotation. FtsI functions in cell wall synthesis specifically during septation. The IBA inference is supported by extensive experimental evidence.
Supporting Evidence:
PMID:6450748
These results support the hypothesis that PBP-3 activity is exclusively required for septal murein synthesis
GO:0000917 division septum assembly
IEA
GO_REF:0000043
ACCEPT
Summary: FtsI is essential for division septum assembly. It localizes to the septum and provides the transpeptidase activity necessary for cross-linking peptidoglycan during septation [PMID:9603865, PMID:28419603].
Reason: Core biological process for FtsI. The IEA annotation based on UniProt keywords is appropriate and supported by extensive experimental evidence from multiple publications.
Supporting Evidence:
PMID:9603865
The localization of FtsI (PBP3), a penicillin-binding protein specifically required for cell division in Escherichia coli, was investigated by immunofluorescence microscopy and found to localize to the septum
PMID:28419603
Cell division in Escherichia coli is mediated by a large protein complex called the divisome
GO:0004180 carboxypeptidase activity
IEA
GO_REF:0000043
ACCEPT
Summary: FtsI has D,D-transpeptidase activity classified under EC 3.4.16.4 (serine-type D-Ala-D-Ala carboxypeptidase). This activity involves cleavage of the D-Ala-D-Ala bond and transpeptidation.
Reason: Appropriate general MF term. FtsI catalyzes the cleavage of the terminal D-alanine from peptidoglycan precursors during transpeptidation, which is a type of carboxypeptidase activity. More specific term GO:0009002 is also annotated.
Supporting Evidence:
PMID:3531167
Activity of penicillin-binding protein 3 from Escherichia coli
GO:0005886 plasma membrane
IEA
GO_REF:0000120
ACCEPT
Summary: Duplicate annotation for plasma membrane localization via combined IEA methods. FtsI is a membrane-anchored protein.
Reason: Correct localization. Duplicates with different evidence codes are acceptable as they provide independent support.
GO:0006508 proteolysis
IEA
GO_REF:0000043
KEEP AS NON CORE
Summary: FtsI has peptidase activity (D,D-transpeptidase) that involves cleavage of peptide bonds in peptidoglycan precursors during cell wall synthesis.
Reason: While technically accurate (FtsI cleaves D-Ala-D-Ala bonds), this is a very broad term. The more specific biological process is peptidoglycan biosynthesis, not general proteolysis. Keep as non-core.
GO:0008233 peptidase activity
IEA
GO_REF:0000043
KEEP AS NON CORE
Summary: FtsI has D,D-transpeptidase activity that involves peptide bond cleavage.
Reason: Accurate but very general. The more specific term GO:0009002 (serine-type D-Ala-D-Ala carboxypeptidase activity) is more informative. Keep as non-core supporting annotation.
GO:0008360 regulation of cell shape
IEA
GO_REF:0000043
MARK AS OVER ANNOTATED
Summary: FtsI is involved in septation-specific peptidoglycan synthesis. While cell division affects cell shape, FtsI is not primarily a shape-regulating protein like PBP2 (which determines rod shape). FtsI specifically functions in division, not elongation.
Reason: Spratt 1975 [PMID:1103132] showed distinct PBPs for division (PBP3/FtsI), elongation (PBP1), and shape (PBP2). FtsI loss causes filamentation but does not alter cell shape in the way PBP2 mutations do. This annotation conflates division with shape regulation.
Supporting Evidence:
PMID:1103132
Cell shape: beta-Lactams that specifically result in the production of ovoid cells bind to penicillin binding protein 2... Cell division: beta-Lactams that specifically inhibit cell division bind preferentially to penicillin binding protein 3
GO:0008658 penicillin binding
IEA
GO_REF:0000120
ACCEPT
Summary: Duplicate annotation for penicillin binding via combined IEA methods.
Reason: Core molecular function. Duplicates with different evidence sources are acceptable.
GO:0008955 peptidoglycan glycosyltransferase activity
IEA
GO_REF:0000002
REMOVE
Summary: INCORRECT ANNOTATION. FtsI is a Class B PBP that lacks glycosyltransferase activity. UniProt explicitly states: "Was originally thought to be a bifunctional enzyme with transglycosylase and transpeptidase activities" (CAUTION). The SEDS protein FtsW provides the glycosyltransferase activity in the FtsI-FtsW complex [PMID:27525505].
Reason: This is a well-documented error. Meeske et al. 2016 [PMID:27525505] clearly state that Class B PBPs "have TP domains but lack PGT activity." The glycosyltransferase activity is provided by SEDS proteins (FtsW for division, RodA for elongation), not by Class B PBPs like FtsI. The InterPro mapping that generated this IEA annotation is incorrect for FtsI.
Supporting Evidence:
PMID:27525505
Under these conditions, cross-linking of adjacent glycan strands is likely carried out by the essential Class B PBPs (for simplicity, bPBPs), which have TP domains but lack PGT activity
GO:0009002 serine-type D-Ala-D-Ala carboxypeptidase activity
IEA
GO_REF:0000120
ACCEPT
Summary: FtsI catalyzes the transpeptidation reaction that cross-links peptidoglycan strands. The EC number 3.4.16.4 describes this activity: "Preferential cleavage: (Ac)2-L-Lys-D-Ala-|-D-Ala. Also transpeptidation of peptidyl-alanyl moieties."
Reason: Core molecular function of FtsI. This is the primary enzymatic activity that FtsI performs - a serine-type D,D-transpeptidase that cleaves D-Ala-D-Ala bonds and catalyzes transpeptidation to cross-link peptidoglycan.
Supporting Evidence:
PMID:3531167
Activity of penicillin-binding protein 3 from Escherichia coli
PMID:7030331
Peptidoglycan synthetic enzyme activities of highly purified penicillin-binding protein 3
GO:0009252 peptidoglycan biosynthetic process
IEA
GO_REF:0000120
ACCEPT
Summary: FtsI is directly involved in peptidoglycan biosynthesis, specifically the cross-linking step at the division septum [PMID:6450748].
Reason: Core biological process. FtsI catalyzes the transpeptidation reaction that cross-links peptidoglycan strands during septal cell wall synthesis. This is UniProt pathway annotation (UPA00219).
Supporting Evidence:
PMID:6450748
Evidence for involvement of penicillin-binding protein 3 in murein synthesis during septation
GO:0016787 hydrolase activity
IEA
GO_REF:0000043
KEEP AS NON CORE
Summary: FtsI has hydrolase activity as part of its transpeptidase mechanism (cleavage of D-Ala-D-Ala bonds).
Reason: Very general term. More specific terms like GO:0009002 are more informative. Keep as non-core ancestor term.
GO:0043093 FtsZ-dependent cytokinesis
IEA
GO_REF:0000104
ACCEPT
Summary: FtsI functions in FtsZ-dependent cell division. FtsI localization to the septum requires prior localization of FtsZ [PMID:9603865].
Reason: Appropriate biological process. FtsI is part of the divisome that assembles on the FtsZ ring scaffold. Localization is dependent on FtsZ [PMID:9603865].
Supporting Evidence:
PMID:9603865
The localization of FtsI was not observed in ftsZ or ftsA mutants, indicating that it was dependent on the prior localization of these proteins
GO:0051301 cell division
IEA
GO_REF:0000120
ACCEPT
Summary: FtsI is essential for cell division. Inhibition causes filamentation and cell death [PMID:1103132].
Reason: Core biological process. FtsI is required for septation and cell division. Well-supported by experimental evidence.
Supporting Evidence:
PMID:1103132
Cell division: beta-Lactams that specifically inhibit cell division bind preferentially to penicillin binding protein 3
GO:0071555 cell wall organization
IEA
GO_REF:0000043
ACCEPT
Summary: Duplicate annotation for cell wall organization via UniProt keyword mapping.
Reason: Appropriate biological process. Duplicates acceptable with different evidence.
GO:0005515 protein binding
IPI
PMID:15774864
Interaction network among Escherichia coli membrane proteins...
MODIFY
Summary: FtsI interacts with FtsQ (P06136) as shown by bacterial two-hybrid analysis [PMID:15774864]. FtsQ is an essential divisome protein.
Reason: The interaction with FtsQ is well-documented but "protein binding" is uninformative. Should be annotated with a more specific term or with extension indicating the interacting partner. However, no suitable GO term exists for "divisome protein binding" so keeping with IPI to specific protein is acceptable.
Proposed replacements: protein binding
Supporting Evidence:
PMID:15774864
Interaction network among Escherichia coli membrane proteins involved in cell division as revealed by bacterial two-hybrid analysis.
GO:0005515 protein binding
IPI
PMID:15774864
Interaction network among Escherichia coli membrane proteins...
ACCEPT
Summary: FtsI interacts with FtsW (P0ABG4) as shown by bacterial two-hybrid analysis [PMID:15774864]. FtsW-FtsI form a core subcomplex of the divisome.
Reason: The FtsI-FtsW interaction is essential for divisome function. FtsW is the lipid II transporter and glycosyltransferase that works with FtsI [PMID:20847002].
Supporting Evidence:
PMID:20847002
The integral membrane FtsW protein and peptidoglycan synthase PBP3 form a subcomplex in Escherichia coli
PMID:15774864
Interaction network among Escherichia coli membrane proteins involved in cell division as revealed by bacterial two-hybrid analysis.
GO:0005515 protein binding
IPI
PMID:15774864
Interaction network among Escherichia coli membrane proteins...
ACCEPT
Summary: FtsI interacts with FtsL (P0AEN4) per bacterial two-hybrid [PMID:15774864].
Reason: FtsL is an essential divisome protein that interacts with FtsI within the FtsQLB complex.
Supporting Evidence:
PMID:15774864
Interaction network among Escherichia coli membrane proteins involved in cell division as revealed by bacterial two-hybrid analysis.
GO:0005515 protein binding
IPI
PMID:15774864
Interaction network among Escherichia coli membrane proteins...
ACCEPT
Summary: FtsI interacts with FtsN (P29131) per bacterial two-hybrid [PMID:15774864]. FtsI is required for FtsN localization to the septum.
Reason: FtsN is recruited to the septum by FtsI [PMID:9282742]. This interaction is functionally important.
Supporting Evidence:
PMID:9282742
FtsN, a late recruit to the septum in Escherichia coli
PMID:15774864
Interaction network among Escherichia coli membrane proteins involved in cell division as revealed by bacterial two-hybrid analysis.
GO:0005515 protein binding
IPI
PMID:15774864
Interaction network among Escherichia coli membrane proteins...
ACCEPT
Summary: FtsI interacts with YmgF (P58034) per bacterial two-hybrid [PMID:15774864].
Reason: YmgF is a small membrane protein that associates with the divisome.
Supporting Evidence:
PMID:15774864
Interaction network among Escherichia coli membrane proteins involved in cell division as revealed by bacterial two-hybrid analysis.
GO:0005515 protein binding
IPI
PMID:17185541
Three functional subdomains of the Escherichia coli FtsQ pro...
ACCEPT
Summary: FtsI interacts with FtsQ (P06136). Study mapped the FtsQ domains involved in interactions with divisome proteins [PMID:17185541].
Reason: Independent confirmation of FtsI-FtsQ interaction using domain mapping.
Supporting Evidence:
PMID:17185541
FtsQ, an essential protein for the Escherichia coli divisome assembly, is able to interact with various division proteins, namely FtsI, FtsL, FtsN, FtsB and FtsW
GO:0005515 protein binding
IPI
PMID:17185541
Three functional subdomains of the Escherichia coli FtsQ pro...
ACCEPT
Summary: Cross-species interaction between E. coli FtsI and S. pneumoniae DivIB.
Reason: Xenologous interaction supporting functional conservation of divisome protein interactions.
Supporting Evidence:
PMID:17185541
Three functional subdomains of the Escherichia coli FtsQ protein are involved in its interaction with the other division proteins.
GO:0005515 protein binding
IPI
PMID:17938168
The essential cell division protein FtsN interacts with the ...
ACCEPT
Summary: FtsI interacts with FtsN per [PMID:17938168]. The study examined FtsN interactions with peptidoglycan synthases.
Reason: Additional evidence for FtsI-FtsN interaction.
Supporting Evidence:
PMID:17938168
2007 Oct 15. The essential cell division protein FtsN interacts with the murein (peptidoglycan) synthase PBP1B in Escherichia coli.
GO:0005515 protein binding
IPI
PMID:18165305
The monofunctional glycosyltransferase of Escherichia coli l...
ACCEPT
Summary: FtsI (PBP3) interacts with PBP1B (P02919/mrcB). PBP1B is a bifunctional Class A PBP with both glycosyltransferase and transpeptidase activity [PMID:18165305].
Reason: PBP1B localizes to the septum and works with FtsI in septal peptidoglycan synthesis. This interaction is functionally important.
Supporting Evidence:
PMID:28233869
In E. coli, the complex formed by PBP1b, PBP3 and FtsW constitutes the core-enzyme of the divisome
PMID:18165305
The monofunctional glycosyltransferase of Escherichia coli localizes to the cell division site and interacts with penicillin-binding protein 3, FtsW, and FtsN.
GO:0005515 protein binding
IPI
PMID:18165305
The monofunctional glycosyltransferase of Escherichia coli l...
ACCEPT
Summary: FtsI interacts with MtgA (P46022), the monofunctional glycosyltransferase [PMID:18165305].
Reason: MtgA localizes to the division site and interacts with PBP3, FtsW, and FtsN, suggesting a role in septal peptidoglycan synthesis.
Supporting Evidence:
PMID:18165305
The monofunctional peptidoglycan glycosyltransferase (MtgA) catalyzes glycan chain elongation... is able to interact with three constituents of the divisome, PBP3, FtsW, and FtsN
GO:0005515 protein binding
IPI
PMID:18978050
Characterization of YmgF, a 72-residue inner membrane protei...
ACCEPT
Summary: FtsI interacts with FtsL. Study characterized YmgF and its association with the division machinery [PMID:18978050].
Reason: Additional evidence for FtsI-FtsL interaction.
Supporting Evidence:
PMID:18978050
Characterization of YmgF, a 72-residue inner membrane protein that associates with the Escherichia coli cell division machinery.
GO:0005515 protein binding
IPI
PMID:18978050
Characterization of YmgF, a 72-residue inner membrane protei...
ACCEPT
Summary: FtsI interacts with YmgF [PMID:18978050].
Reason: YmgF is a component of the E. coli cell division machinery.
Supporting Evidence:
PMID:18978050
Characterization of YmgF, a 72-residue inner membrane protein that associates with the Escherichia coli cell division machinery.
GO:0005515 protein binding
IPI
PMID:19458048
Crystal structure of the membrane-bound bifunctional transgl...
ACCEPT
Summary: FtsI interacts with PBP1B. Crystal structure study of PBP1b [PMID:19458048].
Reason: Supports FtsI-PBP1B interaction.
Supporting Evidence:
PMID:19458048
Crystal structure of the membrane-bound bifunctional transglycosylase PBP1b from Escherichia coli.
GO:0005515 protein binding
IPI
PMID:20847002
The integral membrane FtsW protein and peptidoglycan synthas...
ACCEPT
Summary: FtsI forms a subcomplex with FtsW. FRET and co-immunoprecipitation experiments confirmed direct interactions [PMID:20847002].
Reason: Key evidence for the FtsI-FtsW subcomplex. This is a core interaction for divisome function.
Supporting Evidence:
PMID:20847002
In this work we show direct interactions between FtsW and PBP3 in vivo and in vitro by FRET (FΓΆrster resonance energy transfer) and co-immunoprecipitation experiments
GO:0005515 protein binding
IPI
PMID:22885295
The Ξ²-lactam resistance protein Blr, a small membrane polype...
ACCEPT
Summary: FtsI interacts with FtsL. Study on Blr protein and the division machinery [PMID:22885295].
Reason: Additional evidence for FtsI-FtsL interaction.
Supporting Evidence:
PMID:22885295
The Ξ²-lactam resistance protein Blr, a small membrane polypeptide, is a component of the Escherichia coli cell division machinery.
GO:0005515 protein binding
IPI
PMID:24561554
The binary protein-protein interaction landscape of Escheric...
ACCEPT
Summary: FtsI interacts with MtgA. Large-scale binary protein-protein interaction study [PMID:24561554].
Reason: High-throughput confirmation of FtsI-MtgA interaction.
Supporting Evidence:
PMID:24561554
Here we performed yeast two-hybrid screens of 3,305 baits against 3,606 preys
GO:0000917 division septum assembly
NAS
PMID:28419603
Assembly and activation of the Escherichia coli divisome.
ACCEPT
Summary: FtsI is part of the divisome complex that assembles the division septum. Review article [PMID:28419603].
Reason: Appropriate biological process annotation based on review summarizing extensive experimental literature.
Supporting Evidence:
PMID:28419603
Cell division in Escherichia coli is mediated by a large protein complex called the divisome
GO:0005886 plasma membrane
NAS
PMID:28419603
Assembly and activation of the Escherichia coli divisome.
ACCEPT
Summary: FtsI localizes to the plasma membrane via its N-terminal transmembrane anchor.
Reason: Correct localization annotation.
Supporting Evidence:
PMID:28419603
Assembly and activation of the Escherichia coli divisome.
GO:0032153 cell division site
NAS
PMID:28419603
Assembly and activation of the Escherichia coli divisome.
ACCEPT
Summary: FtsI localizes to the cell division site (septum) during cell division.
Reason: Appropriate cellular component annotation supported by experimental evidence [PMID:9603865].
Supporting Evidence:
PMID:9603865
FtsI and FtsW are localized to the septum in Escherichia coli
PMID:28419603
Assembly and activation of the Escherichia coli divisome.
GO:0043093 FtsZ-dependent cytokinesis
NAS
PMID:28419603
Assembly and activation of the Escherichia coli divisome.
ACCEPT
Summary: FtsI functions in FtsZ-dependent cell division as part of the divisome.
Reason: Appropriate biological process. FtsI localization depends on FtsZ.
Supporting Evidence:
PMID:9603865
The localization of FtsI was not observed in ftsZ or ftsA mutants
PMID:28419603
Assembly and activation of the Escherichia coli divisome.
GO:0051301 cell division
NAS
PMID:28419603
Assembly and activation of the Escherichia coli divisome.
ACCEPT
Summary: FtsI is essential for cell division.
Reason: Core biological process for FtsI.
Supporting Evidence:
PMID:28419603
Assembly and activation of the Escherichia coli divisome.
GO:0005515 protein binding
IPI
PMID:33895137
ZapG (YhcB/DUF1043), a novel cell division protein in gamma-...
ACCEPT
Summary: FtsI interacts with ZapG (YhcB, P0ADW3). ZapG is a novel cell division protein linking the Z-ring to septal peptidoglycan synthesis [PMID:33895137].
Reason: ZapG interacts with multiple divisome components including FtsI, linking the Z-ring scaffold to peptidoglycan synthesis machinery.
Supporting Evidence:
PMID:33895137
ZapG (YhcB/DUF1043), a novel cell division protein in gamma-proteobacteria linking the Z-ring to septal peptidoglycan synthesis
GO:0005515 protein binding
IPI
PMID:28233869
Interplay between Penicillin-binding proteins and SEDS prote...
ACCEPT
Summary: FtsI (PBP3) interacts with FtsW as part of a ternary complex with PBP1b [PMID:28233869]. The study characterized the interplay between these proteins in peptidoglycan synthesis.
Reason: Key evidence showing FtsW-PBP3-PBP1b form a ternary complex essential for divisome function.
Supporting Evidence:
PMID:28233869
PBP3 forms a complex with FtsW and its specific transpeptidase activity is essential for cell division
GO:0009252 peptidoglycan biosynthetic process
RCA
PMID:27525505
SEDS proteins are a widespread family of bacterial cell wall...
ACCEPT
Summary: FtsI participates in peptidoglycan biosynthesis as the transpeptidase that cross-links glycan strands during cell division [PMID:27525505].
Reason: Core biological process. The SEDS paper confirms Class B PBPs like FtsI provide transpeptidase activity for cross-linking.
Supporting Evidence:
PMID:27525505
cross-linking of adjacent glycan strands is likely carried out by the essential Class B PBPs (for simplicity, bPBPs), which have TP domains
GO:0008955 peptidoglycan glycosyltransferase activity
IMP
PMID:6450748
Evidence for involvement of penicillin-binding protein 3 in ...
REMOVE
Summary: INCORRECT ANNOTATION. This 1981 paper predates the discovery that Class B PBPs lack glycosyltransferase activity. The glycosyltransferase activity detected was likely due to contaminating Class A PBPs or the associated SEDS protein FtsW. UniProt explicitly cautions this is an error.
Reason: Historical misattribution. Modern evidence [PMID:27525505] clearly shows Class B PBPs like FtsI lack glycosyltransferase activity. The SEDS protein FtsW (which forms a complex with FtsI) provides this activity. UniProt CAUTION states: "Was originally thought to be a bifunctional enzyme with transglycosylase and transpeptidase activities."
Supporting Evidence:
PMID:27525505
the essential Class B PBPs (for simplicity, bPBPs), which have TP domains but lack PGT activity
PMID:6450748
Evidence for involvement of penicillin-binding protein 3 in murein synthesis during septation but not during cell elongation.
GO:0005515 protein binding
IPI
PMID:20497333
Direct interactions of early and late assembling division pr...
ACCEPT
Summary: FtsI interacts with FtsN. FRET study on divisome protein interactions [PMID:20497333].
Reason: Evidence for FtsI-FtsN interaction.
Supporting Evidence:
PMID:20497333
Epub 2010 May 19. Direct interactions of early and late assembling division proteins in Escherichia coli cells resolved by FRET.
GO:0032153 cell division site
IDA
PMID:9603865
FtsI and FtsW are localized to the septum in Escherichia col...
ACCEPT
Summary: FtsI was shown to localize to the septum by immunofluorescence microscopy [PMID:9603865].
Reason: Core cellular component annotation. Direct experimental evidence (IDA) from immunofluorescence microscopy.
Supporting Evidence:
PMID:9603865
The localization of FtsI (PBP3), a penicillin-binding protein specifically required for cell division in Escherichia coli, was investigated by immunofluorescence microscopy and found to localize to the septum
GO:0008658 penicillin binding
IDA
PMID:1103132
Distinct penicillin binding proteins involved in the divisio...
ACCEPT
Summary: Spratt 1975 demonstrated that beta-lactam antibiotics that specifically inhibit cell division bind to PBP3 (FtsI) [PMID:1103132].
Reason: Core molecular function. Classic paper establishing FtsI as a penicillin- binding protein with direct experimental evidence.
Supporting Evidence:
PMID:1103132
Cell division: beta-Lactams that specifically inhibit cell division bind preferentially to penicillin binding protein 3 (molecular weight 60,000)
GO:0009410 response to xenobiotic stimulus
IMP
PMID:1103132
Distinct penicillin binding proteins involved in the divisio...
KEEP AS NON CORE
Summary: FtsI binds beta-lactam antibiotics (xenobiotics), which inhibit its activity and cause cell filamentation [PMID:1103132].
Reason: While accurate that FtsI responds to beta-lactam antibiotics (xenobiotics), this is not a physiological function but rather a pharmacological property. The response is inhibition of division. Keep as non-core annotation.
Supporting Evidence:
PMID:1103132
beta-Lactams that specifically inhibit cell division bind preferentially to penicillin binding protein 3
GO:0051301 cell division
IMP
PMID:1103132
Distinct penicillin binding proteins involved in the divisio...
ACCEPT
Summary: Temperature-sensitive FtsI mutants fail to divide at non-permissive temperature, demonstrating FtsI is essential for cell division [PMID:1103132].
Reason: Core biological process with strong IMP evidence. Spratt showed that a temperature-sensitive cell division mutant has a thermolabile protein 3.
Supporting Evidence:
PMID:1103132
A temperature-sensitive cell division mutant has been shown to have a thermolabile protein 3
GO:0008955 peptidoglycan glycosyltransferase activity
IDA
PMID:7030331
Peptidoglycan synthetic enzyme activities of highly purified...
REMOVE
Summary: INCORRECT ANNOTATION. This 1981 paper reported glycosyltransferase activity for purified PBP3, but this was later shown to be incorrect. FtsI is a Class B PBP that lacks glycosyltransferase activity. Any detected activity was likely from contaminating enzymes or the associated FtsW.
Reason: Historical misattribution now known to be incorrect. Class B PBPs lack glycosyltransferase (PGT) activity [PMID:27525505]. UniProt states [PMID:7030331] in its CAUTION that FtsI was "originally thought to be a bifunctional enzyme." The glycosyltransferase activity is provided by SEDS proteins (FtsW) or Class A PBPs (PBP1a, PBP1b), not by FtsI.
Supporting Evidence:
PMID:27525505
the essential Class B PBPs (for simplicity, bPBPs), which have TP domains but lack PGT activity
PMID:7030331
Peptidoglycan synthetic enzyme activities of highly purified penicillin-binding protein 3 in Escherichia coli: a septum-forming reaction sequence.

Core Functions

Septal peptidoglycan cross-linking: FtsI catalyzes the transpeptidation reaction that cross-links peptidoglycan strands specifically at the division septum. It is a D,D-transpeptidase (EC 3.4.16.4) that cleaves D-Ala-D-Ala bonds and forms peptide cross-links. This is the primary enzymatic activity of FtsI [PMID:3531167, PMID:7030331].

Penicillin binding: FtsI is one of the major penicillin-binding proteins (PBP3). Beta-lactam antibiotics inhibit FtsI by binding to its active site serine, blocking cell division [PMID:1103132]. This property makes FtsI a key antibiotic target.

Molecular Function:
penicillin binding

References

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Deep Research

Falcon

(ftsI-deep-research-falcon.md)

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πŸ“š Additional Documentation

Bioreason Rl Predictions

(ftsI-bioreason-rl-predictions.md)

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Bioreason Rl Review

(ftsI-bioreason-rl-review.md)

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