Protein profile

PA3596

methylated-DNA--protein-cysteine methyltransferase

Genome: NC_002516.2

Gene: PA3596 Structure source: AlphaFold UniProt Q9HY30

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Amino acids 357

Annotations 11

Features 32

PDB binders 3

Druggability 0.59

Overview

Basic information about this protein and its source genome.

Accession: PA3596
Assembly: Pseudomonas aeruginosa PAO1, complete genome
Gene: PA3596
Status: annotated
Amino acids: 357
Structure source: AlphaFold

2.1.1.63

GO:0003700 A transcription regulator activity that modulates transcription of gene sets via selective and non-covalent binding to a specific double-stranded genomic DNA sequence (sometimes referred to as a motif) within a cis-regulatory region. Regulatory regions include promoters (proximal and distal) and enhancers. Genes are transcriptional units, and include bacterial operons. GO:0003908 Catalysis of the reaction: DNA (containing 6-O-methylguanine) + (protein)-L-cysteine = DNA (without 6-O-methylguanine) + protein S-methyl-L-cysteine. GO:0043565 Binding to DNA of a specific nucleotide composition, e.g. GC-rich DNA binding, or with a specific sequence motif or type of DNA e.g. promotor binding or rDNA binding. GO:0008270 Binding to a zinc ion (Zn). 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. GO:0032259 The process in which a methyl group is covalently attached to a molecule.

Target profile

Computed evidence for target prioritization.

Human off-target: hit
Human identity (%): 31.034
Human E-value: 8.41e-15
Gut microbiome off-target: hit
Essential (DEG): N
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 0.59

Structure –

Pocket –

Sequence

Primary amino-acid sequence viewer.

Functional Annotations

Enzyme classification and Gene Ontology terms linked to this protein.

1 EC 10 GO

Enzyme Commission (EC)

2.1.1.63

Gene Ontology (GO)

GO:0003700 A transcription regulator activity that modulates transcription of gene sets via selective and non-covalent binding to a specific double-stranded genomic DNA sequence (sometimes referred to as a motif) within a cis-regulatory region. Regulatory regions include promoters (proximal and distal) and enhancers. Genes are transcriptional units, and include bacterial operons.
GO:0003908 Catalysis of the reaction: DNA (containing 6-O-methylguanine) + (protein)-L-cysteine = DNA (without 6-O-methylguanine) + protein S-methyl-L-cysteine.
GO:0043565 Binding to DNA of a specific nucleotide composition, e.g. GC-rich DNA binding, or with a specific sequence motif or type of DNA e.g. promotor binding or rDNA binding.
GO:0008270 Binding to a zinc ion (Zn).
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.
GO:0032259 The process in which a methyl group is covalently attached to a molecule.
GO:0006355 Any process that modulates the frequency, rate or extent of cellular DNA-templated transcription.
GO:0003677 Any molecular function by which a gene product interacts selectively and non-covalently with DNA (deoxyribonucleic acid).
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:0008168 Catalysis of the transfer of a methyl group to an acceptor molecule.

Sequence Features

Domain/signature hits from InterPro and related databases.

32 records

Show feature table

Start	End	DB	Term	Name
273	351	CDD	cd06445	ATase
273	351	InterPro	IPR014048	Methylated-DNA-[protein]-cysteine S-methyltransferase, DNA binding
268	353	FunFam	G3DSA:1.10.10.10:FF:000214	Methylated-DNA--protein-cysteine methyltransferase
189	266	Gene3D	G3DSA:3.30.160.70	-
103	184	SMART	SM00342	aracneu4
103	184	InterPro	IPR018060	DNA binding HTH domain, AraC-type
191	274	SUPERFAMILY	SSF53155	Methylated DNA-protein cysteine methyltransferase domain
191	274	InterPro	IPR036631	Methylated DNA-protein cysteine methyltransferase domain superfamily
9	87	SUPERFAMILY	SSF57884	Ada DNA repair protein, N-terminal domain (N-Ada 10)
9	87	InterPro	IPR035451	Ada-like domain superfamily
189	353	PANTHER	PTHR10815	METHYLATED-DNA--PROTEIN-CYSTEINE METHYLTRANSFERASE
16	78	Pfam	PF02805	Metal binding domain of Ada
16	78	InterPro	IPR004026	Ada DNA repair, metal-binding
272	350	NCBIfam	TIGR00589	methylated-DNA--[protein]-cysteine S-methyltransferase
272	350	InterPro	IPR014048	Methylated-DNA-[protein]-cysteine S-methyltransferase, DNA binding
94	187	Gene3D	G3DSA:1.10.10.60	-
268	352	Gene3D	G3DSA:1.10.10.10	-
268	352	InterPro	IPR036388	Winged helix-like DNA-binding domain superfamily
110	186	Pfam	PF12833	Helix-turn-helix domain
110	186	InterPro	IPR018060	DNA binding HTH domain, AraC-type
1	357	PIRSF	PIRSF000409	Ada
1	357	InterPro	IPR016221	Bifunctional regulatory protein Ada
321	327	ProSitePatterns	PS00374	Methylated-DNA--protein-cysteine methyltransferase active site.
321	327	InterPro	IPR001497	Methylated-DNA-[protein]-cysteine S-methyltransferase, active site
10	79	Gene3D	G3DSA:3.40.10.10	DNA Methylphosphotriester Repair Domain
10	79	InterPro	IPR035451	Ada-like domain superfamily
271	351	SUPERFAMILY	SSF46767	Methylated DNA-protein cysteine methyltransferase, C-terminal domain
271	351	InterPro	IPR036217	Methylated DNA-protein cysteine methyltransferase, DNA binding domain
112	186	ProSiteProfiles	PS01124	Bacterial regulatory proteins, araC family DNA-binding domain profile.
112	186	InterPro	IPR018060	DNA binding HTH domain, AraC-type
272	351	Pfam	PF01035	6-O-methylguanine DNA methyltransferase, DNA binding domain
272	351	InterPro	IPR014048	Methylated-DNA-[protein]-cysteine S-methyltransferase, DNA binding

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 PA3596	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
2				0.59
9				0.477
1				0.262

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.

53 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
ETW	6GA0	Q97VW7	479.5 Da LogP 5.21 TPSA 116.8	1 viol.	✓ Clean	`Cc1ccc(cc1)CNC(=O)c2ccc(c(c2)C(=O)O)C3=C4C=CC(=…`
OGQ	6Y8P	E5BBQ0	534.6 Da LogP 5.24 TPSA 85.8	2 viol.	✓ Clean	`Cc1ccc(cc1)CNC(=O)c2ccc(c(c2)C3=C4C=CC(=[N+](C)…`
PBO	3GYH	Q9UTN9	149.2 Da LogP 2.06 TPSA 30.0	✓ Ro5	✓ Clean	`CCCC(=O)c1cccnc1`

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
ZINC100071118	0.758	205.3 Da LogP 3.62 TPSA 30.0	✓ Ro5	✓ Clean	`CCCCCCCC(=O)c1cccnc1`
ZINC100071122	0.758	219.3 Da LogP 4.01 TPSA 30.0	✓ Ro5	✓ Clean	`CCCCCCCCC(=O)c1cccnc1`
ZINC22054134	0.723	431.5 Da LogP 3.70 TPSA 94.0	✓ Ro5	✓ Clean	`CN(C)c1ccc2c(-c3cc(C(=O)O)ccc3C(=O)O)c3ccc(=[N+…`
ZINC5030658	0.683	376.3 Da LogP 3.67 TPSA 125.0	✓ Ro5	✓ Clean	`O=C(O)c1ccc(-c2c3ccc(=O)cc-3oc3cc(O)ccc23)c(C(=…`
ZINC28630842	0.681	489.5 Da LogP 4.34 TPSA 154.1	✓ Ro5	✓ Clean	`O=C(O)CCCCCNC(=O)c1ccc(-c2c3ccc(=O)cc-3oc3cc(O)…`
ZINC100083979	0.667	226.2 Da LogP 1.93 TPSA 59.9	✓ Ro5	✓ Clean	`O=C(CC(=O)c1cccnc1)c1cccnc1`
ZINC2379080	0.667	207.2 Da LogP 1.61 TPSA 56.3	✓ Ro5	✓ Clean	`CCOC(=O)CCC(=O)c1cccnc1`
ZINC70915012	0.647	203.2 Da LogP 2.61 TPSA 30.0	✓ Ro5	✓ Clean	`O=C(CCC(F)(F)F)c1cccnc1`
ZINC2379083	0.632	221.3 Da LogP 2.00 TPSA 56.3	✓ Ro5	✓ Clean	`CCOC(=O)CCCC(=O)c1cccnc1`
ZINC34274984	0.629	211.3 Da LogP 2.90 TPSA 30.0	✓ Ro5	✓ Clean	`O=C(CCc1ccccc1)c1cccnc1`
ZINC100077468	0.625	225.2 Da LogP 2.54 TPSA 47.0	✓ Ro5	✓ Clean	`O=C(CC(=O)c1cccnc1)c1ccccc1`
ZINC169722656	0.622	458.4 Da LogP 4.40 TPSA 165.6	✓ Ro5	Alert	`[N-]=[N+]=NCCCNC(=O)c1ccc(C(=O)O)c(-c2c3ccc(=O)…`
ZINC161862	0.611	211.3 Da LogP 2.82 TPSA 30.0	✓ Ro5	✓ Clean	`Cc1ccc(CC(=O)c2cccnc2)cc1`
ZINC37992322	0.611	211.3 Da LogP 2.82 TPSA 30.0	✓ Ro5	✓ Clean	`Cc1ccccc1CC(=O)c1cccnc1`
ZINC5248684	0.594	376.3 Da LogP 3.67 TPSA 125.0	✓ Ro5	✓ Clean	`O=C(O)c1ccc(C(=O)O)c(-c2c3ccc(=O)cc-3oc3cc(O)cc…`
ZINC6562820	0.590	220.3 Da LogP 1.52 TPSA 50.3	✓ Ro5	✓ Clean	`CC(=O)N(C)CCCC(=O)c1cccnc1`
ZINC3872582	0.587	332.3 Da LogP 3.97 TPSA 87.7	✓ Ro5	✓ Clean	`O=C(O)c1ccccc1-c1c2ccc(=O)cc-2oc2cc(O)ccc12`
ZINC1592410	0.586	212.2 Da LogP 1.54 TPSA 59.9	✓ Ro5	Alert	`O=C(C(=O)c1cccnc1)c1cccnc1`
ZINC100103222	0.583	217.1 Da LogP 1.79 TPSA 47.0	✓ Ro5	✓ Clean	`O=C(CC(=O)C(F)(F)F)c1cccnc1`
ZINC394078	0.583	206.3 Da LogP 2.34 TPSA 33.2	✓ Ro5	✓ Clean	`CCCN(CCC)C(=O)c1cccnc1`
ZINC4430794	0.583	205.3 Da LogP 2.27 TPSA 47.0	✓ Ro5	✓ Clean	`CC(C)(C)C(=O)CC(=O)c1cccnc1`
ZINC84193868	0.583	213.2 Da LogP 2.21 TPSA 50.2	✓ Ro5	✓ Clean	`O=C(Cc1ccc(O)cc1)c1cccnc1`
ZINC238651069	0.579	208.2 Da LogP 0.46 TPSA 93.3	✓ Ro5	✓ Clean	`N[C@H](CCC(=O)c1cccnc1)C(=O)O`
ZINC238665102	0.579	208.2 Da LogP 0.46 TPSA 93.3	✓ Ro5	✓ Clean	`N[C@@H](CCC(=O)c1cccnc1)C(=O)O`
ZINC303011	0.575	283.3 Da LogP 3.07 TPSA 71.1	✓ Ro5	✓ Clean	`CCCC(=O)Nc1ccc(NC(=O)c2cccnc2)cc1`
ZINC5239470	0.575	207.2 Da LogP 1.66 TPSA 62.6	✓ Ro5	✓ Clean	`CN(CCCC(=O)c1cccnc1)N=O`
ZINC5030632	0.571	332.3 Da LogP 3.97 TPSA 87.7	✓ Ro5	✓ Clean	`O=C(O)c1ccc(-c2c3ccc(=O)cc-3oc3cc(O)ccc23)cc1`
ZINC100035725	0.569	473.4 Da LogP 3.19 TPSA 151.4	✓ Ro5	✓ Clean	`O=C(ON1C(=O)CCC1=O)c1ccc(-c2c3ccc(=O)cc-3oc3cc(…`
ZINC25762071	0.569	362.3 Da LogP 3.13 TPSA 139.8	✓ Ro5	✓ Clean	`Nc1cc(C(=O)O)c(-c2c3ccc(=O)cc-3oc3cc(O)ccc23)cc…`
ZINC100003502	0.568	207.2 Da LogP 0.40 TPSA 73.3	✓ Ro5	✓ Clean	`COC(=O)C(=O)CC(=O)c1cccnc1`
ZINC37992319	0.568	231.7 Da LogP 3.16 TPSA 30.0	✓ Ro5	✓ Clean	`O=C(Cc1ccc(Cl)cc1)c1cccnc1`
ZINC37992320	0.568	215.2 Da LogP 2.65 TPSA 30.0	✓ Ro5	✓ Clean	`O=C(Cc1ccc(F)cc1)c1cccnc1`
ZINC37992321	0.568	276.1 Da LogP 3.27 TPSA 30.0	✓ Ro5	✓ Clean	`O=C(Cc1ccc(Br)cc1)c1cccnc1`
ZINC100083975	0.564	267.3 Da LogP 3.46 TPSA 47.0	✓ Ro5	✓ Clean	`Cc1cc(C)c(C(=O)CC(=O)c2cccnc2)c(C)c1`
ZINC100085501	0.564	221.2 Da LogP 0.79 TPSA 73.3	✓ Ro5	✓ Clean	`CCOC(=O)C(=O)CC(=O)c1cccnc1`
ZINC37464014	0.564	211.3 Da LogP 2.82 TPSA 30.0	✓ Ro5	✓ Clean	`Cc1cccc(CC(=O)c2cccnc2)c1`
ZINC38125314	0.564	227.3 Da LogP 2.52 TPSA 39.2	✓ Ro5	✓ Clean	`COc1ccc(CC(=O)c2cccnc2)cc1`
ZINC22063503	0.561	221.3 Da LogP 2.05 TPSA 62.6	✓ Ro5	✓ Clean	`CN(CCCCC(=O)c1cccnc1)N=O`
ZINC1667326	0.553	384.4 Da LogP 1.90 TPSA 112.5	✓ Ro5	✓ Clean	`CCOC(=O)[C@H](C(=O)c1cccnc1)[C@H](C(=O)OCC)C(=O…`
ZINC1667329	0.553	384.4 Da LogP 1.90 TPSA 112.5	✓ Ro5	✓ Clean	`CCOC(=O)[C@@H](C(=O)c1cccnc1)[C@@H](C(=O)OCC)C(…`
ZINC17299137	0.553	384.4 Da LogP 1.90 TPSA 112.5	✓ Ro5	✓ Clean	`CCOC(=O)[C@H](C(=O)c1cccnc1)[C@@H](C(=O)OCC)C(=…`
ZINC2765515	0.553	234.3 Da LogP 3.12 TPSA 33.2	✓ Ro5	✓ Clean	`CCCCN(CCCC)C(=O)c1cccnc1`
ZINC36941212	0.553	225.3 Da LogP 3.27 TPSA 30.0	✓ Ro5	✓ Clean	`CCCc1ccc(C(=O)c2cccnc2)cc1`
ZINC380074941	0.550	222.2 Da LogP 0.66 TPSA 88.9	✓ Ro5	✓ Clean	`COC(=O)C(CC(=O)c1cccnc1)=NO`
ZINC88616762	0.550	222.2 Da LogP 0.66 TPSA 88.9	✓ Ro5	✓ Clean	`COC(=O)/C(CC(=O)c1cccnc1)=N/O`
ZINC575443691	0.548	268.4 Da LogP 3.18 TPSA 33.2	✓ Ro5	✓ Clean	`CN(CCCC(=O)c1cccnc1)Cc1ccccc1`
ZINC584908924	0.548	251.3 Da LogP 1.62 TPSA 65.5	✓ Ro5	✓ Clean	`COCCCOC(=O)CCC(=O)c1cccnc1`
ZINC45028802	0.543	211.3 Da LogP 2.93 TPSA 30.0	✓ Ro5	✓ Clean	`Cc1cccc(C)c1C(=O)c1cccnc1`
ZINC25781561	0.542	421.4 Da LogP 3.13 TPSA 137.8	✓ Ro5	✓ Clean	`NNC(=S)Nc1ccc(-c2c3ccc(=O)cc-3oc3cc(O)ccc23)c(C…`
ZINC22121726	0.541	211.3 Da LogP 2.88 TPSA 30.0	✓ Ro5	✓ Clean	`CCc1ccc(C(=O)c2cccnc2)cc1`

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.