Target Pathogen

Overview

Basic information about this protein and its source genome.

Accession: PA3495
Assembly: Pseudomonas aeruginosa PAO1, complete genome
Gene: PA3495 nth
Status: annotated
Amino acids: 212
Structure source: AlphaFold

EC

4.2.99.18

GO

GO:0051539 Binding to a 4 iron, 4 sulfur (4Fe-4S) cluster; this cluster consists of four iron atoms, with the inorganic sulfur atoms found between the irons and acting as bridging ligands. GO:0140078 Catalysis of the cleavage of an AP site 3' of the baseless site by a beta-lyase mechanism, leaving an unsaturated aldehyde, termed a 3'-(4-hydroxy-5-phospho-2-pentenal) residue, and a 5'-phosphate. GO:0003677 Any molecular function by which a gene product interacts selectively and non-covalently with DNA (deoxyribonucleic acid). GO:0019104 Catalysis of the removal of damaged bases by cleaving the N-C1' glycosidic bond between the target damaged DNA base and the deoxyribose sugar. The reaction releases a free base and leaves an apurinic/apyrimidinic (AP) site. GO:0046872 Binding to a metal ion. GO:0006285 The formation of an AP site, a deoxyribose sugar with a missing base, by DNA glycosylase which recognizes an altered base in DNA and catalyzes its hydrolytic removal. This sugar phosphate is the substrate recognized by the AP endonuclease, which cuts the DNA phosphodiester backbone at the 5' side of the altered site to leave a gap which is subsequently repaired.

Target profile

Computed evidence for target prioritization.

Human off-target: hit
Human identity (%): 33.871
Human E-value: 3.83e-14
Gut microbiome off-target: hit
Essential (DEG): Y
Localization: Cytoplasmic

Selected Druggability evidence

Selected Druggability is the FPocket score chosen for ranking using the curated structure priority. The 3D viewer may show a different loaded structure, so its visible pockets can differ.

FPocket 0.67

Structure –

Pocket –

Sequence

Primary amino-acid sequence viewer.

MNAAKRAEIFRRLHEDNPEPRTELAYTTPFELLIAVILSAQATDVGVNKATARLYPVANTPEAIHALGVEGLSEYIKTIGLYNSKAKNVIETCRILIEKHGGQVPDNREDLEALPGVGRKTANVVLNTAFRQLAMAVDTHIFRVANRTGIAPGKNVLEVEKKLLKFVPREYLLDAHHWLILHGRYVCKARKPQCGSCRIEDLCEYKHKTSDD

Functional Annotations

Enzyme classification and Gene Ontology terms linked to this protein.

1 EC 10 GO

Enzyme Commission (EC)

1

4.2.99.18

Gene Ontology (GO)

10

GO:0051539 Binding to a 4 iron, 4 sulfur (4Fe-4S) cluster; this cluster consists of four iron atoms, with the inorganic sulfur atoms found between the irons and acting as bridging ligands.
GO:0140078 Catalysis of the cleavage of an AP site 3' of the baseless site by a beta-lyase mechanism, leaving an unsaturated aldehyde, termed a 3'-(4-hydroxy-5-phospho-2-pentenal) residue, and a 5'-phosphate.
GO:0003677 Any molecular function by which a gene product interacts selectively and non-covalently with DNA (deoxyribonucleic acid).
GO:0019104 Catalysis of the removal of damaged bases by cleaving the N-C1' glycosidic bond between the target damaged DNA base and the deoxyribose sugar. The reaction releases a free base and leaves an apurinic/apyrimidinic (AP) site.
GO:0046872 Binding to a metal ion.
GO:0006285 The formation of an AP site, a deoxyribose sugar with a missing base, by DNA glycosylase which recognizes an altered base in DNA and catalyzes its hydrolytic removal. This sugar phosphate is the substrate recognized by the AP endonuclease, which cuts the DNA phosphodiester backbone at the 5' side of the altered site to leave a gap which is subsequently repaired.
GO:0003906 Catalysis of the cleavage of the C-O-P bond in the AP site created when DNA glycosylase removes a damaged base, involved in the DNA base excision repair pathway (BER).
GO:0006284 In base excision repair, an altered base is removed by a DNA glycosylase enzyme, followed by excision of the resulting sugar phosphate. The small gap left in the DNA helix is filled in by the sequential action of DNA polymerase and DNA ligase.
GO:0003824 Catalysis of a biochemical reaction at physiological temperatures. In biologically catalyzed reactions, the reactants are known as substrates, and the catalysts are naturally occurring macromolecular substances known as enzymes. Enzymes possess specific binding sites for substrates, and are usually composed wholly or largely of protein, but RNA that has catalytic activity (ribozyme) is often also regarded as enzymatic.
GO:0006281 The process of restoring DNA after damage. Genomes are subject to damage by chemical and physical agents in the environment (e.g. UV and ionizing radiations, chemical mutagens, fungal and bacterial toxins, etc.) and by free radicals or alkylating agents endogenously generated in metabolism. DNA is also damaged because of errors during its replication. A variety of different DNA repair pathways have been reported that include direct reversal, base excision repair, nucleotide excision repair, photoreactivation, bypass, double-strand break repair pathway, and mismatch repair pathway.

Sequence Features

Domain/signature hits from InterPro and related databases.

25 records

Show feature table

Start	End	DB	Term	Name
186	206	SMART	SM00525	ccc3
186	206	InterPro	IPR003651	Endonuclease III-like, iron-sulphur cluster loop motif
5	194	NCBIfam	TIGR01083	endonuclease III
5	194	InterPro	IPR005759	Endonuclease III
30	183	CDD	cd00056	ENDO3c
30	183	InterPro	IPR003265	HhH-GPD domain
3	208	SUPERFAMILY	SSF48150	DNA-glycosylase
3	208	InterPro	IPR011257	DNA glycosylase
1	209	Hamap	MF_00942	Endonuclease III [nth].
1	209	InterPro	IPR005759	Endonuclease III
187	203	Pfam	PF10576	Iron-sulfur binding domain of endonuclease III
187	203	InterPro	IPR003651	Endonuclease III-like, iron-sulphur cluster loop motif
1	212	PIRSF	PIRSF001435	Nth
21	132	Gene3D	G3DSA:1.10.340.30	Hypothetical protein; domain 2
100	127	Pfam	PF00633	Helix-hairpin-helix motif
100	127	InterPro	IPR000445	Helix-hairpin-helix motif
2	210	PANTHER	PTHR10359	A/G-SPECIFIC ADENINE GLYCOSYLASE/ENDONUCLEASE III
127	205	FunFam	G3DSA:1.10.1670.10:FF:000001	Endonuclease III
38	185	SMART	SM00478	endo3end
38	185	InterPro	IPR003265	HhH-GPD domain
12	205	Gene3D	G3DSA:1.10.1670.10	-
12	205	InterPro	IPR023170	Helix-hairpin-helix, base-excision DNA repair, C-terminal
21	132	FunFam	G3DSA:1.10.340.30:FF:000001	Endonuclease III
34	168	Pfam	PF00730	HhH-GPD superfamily base excision DNA repair protein
34	168	InterPro	IPR003265	HhH-GPD domain

3D Structure

Selected loaded structure. Experimental PDB entries may cover only a portion of the sequence; predicted models typically cover the full protein.

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Structural evidence

0 + 1

Experimental PDB entries and predicted models. Click Switch to display a different structure in the viewer.

Entry	Method	Resolution	Chain	Coverage	Links	Status
AlphaFold PA3495	AlphaFold	—	—	full sequence	—	Viewing

Pocket details FPocket · P2Rank — toggle visibility and zoom from here, or open full viewer

Pockets (FPOCKET)

Showing top-ranked FPocket candidates by druggability. Druggability is color-coded: high (0.7 or higher), medium (0.4 to 0.69), low (below 0.4).

FPOCKET	Sticks	Spheres	Surfaces	Druggability	Labels	Zoom	Positions
1				0.67

Ligand evidence

Ligands grouped by evidence source. PDB ligands keep the source crystal visible, and loaded crystals can be opened directly in the structure viewer.

5 records

Highest-confidence structural evidence: ligands co-crystallized with this exact protein. If the source PDB is loaded in TPW, use Open crystal to inspect it in the structure viewer.

No PDB structure with a co-crystallized ligand found for this exact protein.

Structural evidence inferred from similar proteins. The source crystal indicates where the ligand was observed; the UniProt column identifies the homologous protein carrying that ligand.

Ligand	Source crystal	UniProt (homolog)	MW · LogP · TPSA	Lipinski	PAINS	SMILES
ADE	1MUD	P17802	135.1 Da LogP -0.06 TPSA 80.5	✓ Ro5	✓ Clean	`c1[nH]c2c(n1)c(ncn2)N`

Experimental bioactivity from ChEMBL measured directly on this protein. Score = pchembl (−log Ki/IC₅₀; higher = more potent).

No ChEMBL bioactivity data found for this exact protein.

Bioactivity inferred from similar proteins in ChEMBL. Score = pchembl (−log Ki/IC₅₀; higher = more potent).

No ChEMBL hits found through similar proteins.

Proposed virtual-screening candidates from ZINC. Score = Tanimoto similarity to a known binder (0–1; higher = more similar).

Ligand	Tanimoto	MW · LogP · TPSA	Lipinski	PAINS	SMILES
ZINC43463386	0.533	261.0 Da LogP 0.54 TPSA 80.5	✓ Ro5	✓ Clean	`Nc1nc(I)nc2[nH]cnc12`
ZINC4552271	0.533	237.5 Da LogP 2.18 TPSA 54.5	✓ Ro5	✓ Clean	`ClC(Cl)(Cl)c1ncnc2[nH]cnc12`
ZINC4707072	0.533	214.0 Da LogP 0.70 TPSA 80.5	✓ Ro5	✓ Clean	`Nc1nc(Br)nc2[nH]cnc12`
ZINC5543260	0.500	200.2 Da LogP -0.40 TPSA 108.8	✓ Ro5	✓ Clean	`O=S(=O)(O)c1ncnc2[nH]cnc12`

PDB and ChEMBL records on this protein are shown in full. ChEMBL records from similar proteins are capped at the top 100 per protein (by pchembl) and ZINC at the top 50 (Tanimoto ≥ 0.5). ADME columns are descriptor-based screening flags, not experimental toxicity results.

PA3495