Protein profile

PA4228

2,3-dihydroxybenzoate-AMP ligase

Genome: NC_002516.2

Gene: pchD PA4228 Structure source: Experimental + AlphaFold UniProt Q9HWG3

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Amino acids 547

Annotations 3

Features 17

PDB binders 12

Druggability 0.642

Overview

Basic information about this protein and its source genome.

Accession: PA4228
Assembly: Pseudomonas aeruginosa PAO1, complete genome
Gene: pchD PA4228
Status: annotated
Amino acids: 547
Structure source: Experimental + AlphaFold

6.2.1.61

GO:0016878 Catalysis of the joining of an acid and a thiol via a carbon-sulfur bond, with the concomitant hydrolysis of the diphosphate bond in ATP or a similar triphosphate. GO:0017000 The chemical reactions and pathways resulting in the formation of an antibiotic, a substance produced by or derived from certain fungi, bacteria, and other organisms, that can destroy or inhibit the growth of other microorganisms.

Target profile

Computed evidence for target prioritization.

Human off-target: hit
Human identity (%): 36.97
Human E-value: 3.860000000000001e-21
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 0.642

Structure –

Pocket –

Sequence

Primary amino-acid sequence viewer.

MTSSPVTPSAVDDAPDWPAAFVRRYLDAGHWQDQSFAEALATSAARHPRRIALCDDDQRLSYADLLQRCRRLAAGLRQAGLAHGDTVVLHLPNGIAFVETCFALFQLGVRPVLALPAHRQHEISGFCRFAEAKAYIGAERIDGFDPRPMARELLASGACRMALIHGEAEAPLQALAPLYQADALEDCAARAEDIACFQLSGGTTGTPKLIPRRHREYLYNVRASAEVCGFDEHTVYLTGLPMAHNFTLCCPGVIGTLLASGRVVVSQRADPEHCFALIARERVTHTALVPPLAMLWLDAQESRRADLSSLRLLQVGGSRLGSSAAQRVEPVLGCQLQQVLGMAEGLICYTRLDDPPERVLHTQGRPLSPDDEVRVVDAEGREVGPGEVGELTVRGPYTIRGYYRLPEHNAKAFSADGFYRTGDRVSRDKDGYLVVEGRDKDQINRGGEKIAAEEVENLLIAHPQVHDATVVAMPDSLLGERTCAFVIPRQPAPSALKLKQYLHACGLAAFKVPDRIELVPAFPQTGIGKISKKDLRERLRRELEARA

Functional Annotations

Enzyme classification and Gene Ontology terms linked to this protein.

1 EC 2 GO

Enzyme Commission (EC)

6.2.1.61

Gene Ontology (GO)

GO:0016878 Catalysis of the joining of an acid and a thiol via a carbon-sulfur bond, with the concomitant hydrolysis of the diphosphate bond in ATP or a similar triphosphate.
GO:0017000 The chemical reactions and pathways resulting in the formation of an antibiotic, a substance produced by or derived from certain fungi, bacteria, and other organisms, that can destroy or inhibit the growth of other microorganisms.

Sequence Features

Domain/signature hits from InterPro and related databases.

17 records

Show feature table

Start	End	DB	Term	Name
21	541	SUPERFAMILY	SSF56801	Acetyl-CoA synthetase-like
33	538	PANTHER	PTHR43767	LONG-CHAIN-FATTY-ACID--COA LIGASE
440	545	Gene3D	G3DSA:3.30.300.30	-
440	545	InterPro	IPR045851	AMP-binding enzyme, C-terminal domain superfamily
41	445	Pfam	PF00501	AMP-binding enzyme
41	445	InterPro	IPR000873	AMP-dependent synthetase/ligase domain
191	363	FunFam	G3DSA:3.40.50.980:FF:000003	Vibriobactin-specific 2,3-dihydroxybenzoate-AMP ligase
364	438	Gene3D	G3DSA:2.30.38.10	Luciferase; Domain 3
364	438	FunFam	G3DSA:2.30.38.10:FF:000003	Vibriobactin-specific 2,3-dihydroxybenzoate-AMP ligase
454	529	Pfam	PF13193	AMP-binding enzyme C-terminal domain
454	529	InterPro	IPR025110	AMP-binding enzyme, C-terminal domain
197	208	ProSitePatterns	PS00455	Putative AMP-binding domain signature.
197	208	InterPro	IPR020845	AMP-binding, conserved site
440	543	FunFam	G3DSA:3.30.300.30:FF:000008	2,3-dihydroxybenzoate-AMP ligase
20	534	CDD	cd05920	23DHB-AMP_lg
192	363	Gene3D	G3DSA:3.40.50.980	-
31	191	Gene3D	G3DSA:3.40.50.980	-

3D Structure

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

Loading 3D structure...

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Structural evidence

2 + 1

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

Entry	Method	Resolution	Chain	Coverage	Links	Status
PDB 7TZ4	X-ray	1.69 Å	A	100.0% 1-547	PDBe RCSB PDBj File	Viewing
PDB 7TYB	X-ray	2.11 Å	A	100.0% 1-547	PDBe RCSB PDBj File	Loaded
AlphaFold PA4228	AlphaFold	—	—	full sequence	—	Loaded

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				0.642

Pockets (P2RANK)

Showing top-ranked P2Rank candidates by probability. Probability is color-coded per P2Rank calibration: high (≥ 0.5), medium (0.2 – 0.49), low (< 0.2).

P2RANK	Score	Probability
1	64.82	0.99
2	4.41	0.186
3	1.77	0.032
4	1.33	0.015

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				0.754

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.

65 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
1HZ	4IZ6	P10378	466.5 Da LogP -1.40 TPSA 205.9	2 viol.	Alert	`c1cc(c(c(c1)O)O)CCS(=O)(=O)NC[C@@H]2[C@H]([C@H]…`
B1U	6IYK	P10378	495.4 Da LogP -1.37 TPSA 234.9	1 viol.	✓ Clean	`c1ccc(c(c1)C(=O)NS(=O)(=O)OC[C@@H]2[C@H]([C@H](…`
B1X	6IYL	P10378	475.4 Da LogP -1.41 TPSA 215.6	1 viol.	✓ Clean	`c1cc(cc(c1)C(=O)NS(=O)(=O)OCC2C(C(C(O2)n3cnc4c3…`
B5M	5WM4	A0A140DJY3	481.4 Da LogP 0.02 TPSA 212.4	1 viol.	✓ Clean	`Cc1cccc(c1C(=O)OP(=O)(O)OC[C@H]2[C@H]([C@H]([C@…`
B5V	5WM3	A0A140DJY3	467.3 Da LogP -0.29 TPSA 212.4	1 viol.	✓ Clean	`c1ccc(c(c1)C(=O)OP(=O)(O)OC[C@H]2[C@H]([C@H]([C…`
B5Y	5WM5	A0A140DJY3	481.4 Da LogP 0.02 TPSA 212.4	1 viol.	✓ Clean	`Cc1ccc(c(c1)C(=O)OP(=O)(O)OC[C@H]2[C@H]([C@H]([…`
DBH	1MD9	P40871	154.1 Da LogP 0.80 TPSA 77.8	✓ Ro5	Alert	`c1cc(c(c(c1)O)O)C(=O)O`
J2J	6E97	Q47NR5	483.3 Da LogP -0.59 TPSA 232.6	2 viol.	Alert	`c1cc(c(c(c1)O)O)C(=O)OP(=O)(O)OC[C@@H]2[C@H]([C…`
OOB	5WM6	A0A140DJY3	451.3 Da LogP 0.00 TPSA 192.1	1 viol.	✓ Clean	`c1ccc(cc1)C(=O)OP(=O)(O)OC[C@@H]2[C@H]([C@H]([C…`
PNS	3RG2	P10378	358.4 Da LogP -0.96 TPSA 145.2	1 viol.	✓ Clean	`CC(C)(COP(=O)(O)O)[C@H](C(=O)NCCC(=O)NCCS)O`
SAL	5WM2	A0A140DJY3	138.1 Da LogP 1.09 TPSA 57.5	✓ Ro5	✓ Clean	`c1ccc(c(c1)C(=O)O)O`
SVS	3RG2	P10378	450.5 Da LogP -1.10 TPSA 185.7	1 viol.	✓ Clean	`c1ccc(c(c1)CCS(=O)(=O)NC[C@@H]2[C@H]([C@H]([C@@…`

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

Ligand	pchembl	MW · LogP · TPSA	Lipinski	PAINS	SMILES
CHEMBL371502	7.90	466.4 Da LogP -1.58 TPSA 212.0	1 viol.	✓ Clean	`Nc1ncnc2c1ncn2[C@@H]1O[C@H](COS(=O)(=O)NC(=O)c2…`

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

Ligand	UniProt (homolog)	pchembl	MW · LogP · TPSA	Lipinski	PAINS	SMILES
CHEMBL1161845	P10378	8.35	483.3 Da LogP -0.66 TPSA 218.6	2 viol.	Alert	`O=C(NOP(=O)(O)OC[C@H]1O[C@@H](n2cnc3cncnc32)[C@…`
CHEMBL1161846	P10378	7.43	467.3 Da LogP -0.37 TPSA 198.4	1 viol.	✓ Clean	`O=C(NOP(=O)(O)OC[C@H]1O[C@@H](n2cnc3cncnc32)[C@…`

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
ZINC28567519	0.735	466.4 Da LogP -1.00 TPSA 215.5	1 viol.	✓ Clean	`Nc1ncnc2c1ncn2[C@@H]1O[C@H](COS(=O)(=O)/N=C(\O)…`
ZINC14967098	0.727	403.4 Da LogP -3.64 TPSA 217.8	1 viol.	✓ Clean	`NCC(=O)NS(=O)(=O)OC[C@H]1O[C@@H](n2cnc3c(N)ncnc…`
ZINC218033334	0.727	403.4 Da LogP -3.64 TPSA 217.8	1 viol.	✓ Clean	`NCC(=O)NS(=O)(=O)OC[C@H]1O[C@@H](n2cnc3c(N)ncnc…`
ZINC218033425	0.727	403.4 Da LogP -3.64 TPSA 217.8	1 viol.	✓ Clean	`NCC(=O)NS(=O)(=O)OC[C@H]1O[C@@H](n2cnc3c(N)ncnc…`
ZINC218033503	0.727	403.4 Da LogP -3.64 TPSA 217.8	1 viol.	✓ Clean	`NCC(=O)NS(=O)(=O)OC[C@H]1O[C@@H](n2cnc3c(N)ncnc…`
ZINC12405780	0.694	346.3 Da LogP -2.75 TPSA 188.7	1 viol.	✓ Clean	`Nc1ncnc2c1ncn2[C@@H]1O[C@H](COS(N)(=O)=O)[C@@H]…`
ZINC12502832	0.694	346.3 Da LogP -2.75 TPSA 188.7	1 viol.	✓ Clean	`Nc1ncnc2c1ncn2[C@@H]1O[C@H](COS(N)(=O)=O)[C@@H]…`
ZINC79460727	0.694	346.3 Da LogP -2.75 TPSA 188.7	1 viol.	✓ Clean	`Nc1ncnc2c1ncn2[C@@H]1O[C@H](COS(N)(=O)=O)[C@H](…`
ZINC79460732	0.694	346.3 Da LogP -2.75 TPSA 188.7	1 viol.	✓ Clean	`Nc1ncnc2c1ncn2[C@@H]1O[C@H](COS(N)(=O)=O)[C@H](…`
ZINC1083817667	0.667	459.5 Da LogP -2.22 TPSA 217.8	1 viol.	✓ Clean	`CC(C)C[C@@H](N)C(=O)NS(=O)(=O)OC[C@H]1O[C@@H](n…`
ZINC936069043	0.667	459.5 Da LogP -2.22 TPSA 217.8	1 viol.	✓ Clean	`CC[C@@H](C)[C@@H](N)C(=O)NS(=O)(=O)OC[C@@H]1O[C…`
ZINC936069053	0.667	459.5 Da LogP -2.22 TPSA 217.8	1 viol.	✓ Clean	`CC(C)C[C@@H](N)C(=O)NS(=O)(=O)OC[C@@H]1O[C@H](n…`
ZINC168710640	0.658	474.5 Da LogP -4.00 TPSA 260.9	2 viol.	✓ Clean	`NC(=O)CC[C@H](N)C(=O)NS(=O)(=O)OC[C@H]1O[C@@H](…`
ZINC168710738	0.658	474.5 Da LogP -4.00 TPSA 260.9	2 viol.	✓ Clean	`NC(=O)CC[C@H](N)C(=O)NS(=O)(=O)OC[C@H]1O[C@@H](…`
ZINC149361708	0.654	230.2 Da LogP 2.46 TPSA 77.8	✓ Ro5	✓ Clean	`O=C(O)c1cccc(-c2ccccc2O)c1O`
ZINC3869683	0.643	278.4 Da LogP -1.08 TPSA 98.7	✓ Ro5	✓ Clean	`CC(C)(CO)[C@H](O)C(=O)NCCC(=O)NCCS`
ZINC3869684	0.643	278.4 Da LogP -1.08 TPSA 98.7	✓ Ro5	✓ Clean	`CC(C)(CO)[C@@H](O)C(=O)NCCC(=O)NCCS`
ZINC2507163	0.640	217.0 Da LogP 1.85 TPSA 57.5	✓ Ro5	✓ Clean	`O=C(O)c1cccc(Br)c1O`
ZINC39205468	0.640	264.0 Da LogP 1.70 TPSA 57.5	✓ Ro5	✓ Clean	`O=C(O)c1cccc(I)c1O`
ZINC203993915	0.630	204.2 Da LogP 1.95 TPSA 77.8	✓ Ro5	✓ Clean	`O=C(O)c1ccc2cccc(O)c2c1O`
ZINC6524939	0.615	288.3 Da LogP 2.08 TPSA 115.1	✓ Ro5	✓ Clean	`O=C(O)c1cccc(Cc2cccc(C(=O)O)c2O)c1O`
ZINC1701228	0.609	248.2 Da LogP 1.65 TPSA 115.1	✓ Ro5	✓ Clean	`O=C(O)c1ccc2c(O)c(C(=O)O)ccc2c1O`
ZINC1574270	0.606	421.4 Da LogP -0.26 TPSA 162.7	1 viol.	✓ Clean	`Cc1ccc(S(=O)(=O)OC[C@@H]2O[C@H](n3cnc4c(N)ncnc4…`
ZINC3861767	0.606	421.4 Da LogP -0.26 TPSA 162.7	1 viol.	✓ Clean	`Cc1ccc(S(=O)(=O)OC[C@H]2O[C@@H](n3cnc4c(N)ncnc4…`
ZINC82369423	0.600	217.0 Da LogP 1.85 TPSA 57.5	✓ Ro5	✓ Clean	`O=C(O)c1cccc(O)c1Br`
ZINC95713705	0.600	264.0 Da LogP 1.70 TPSA 57.5	✓ Ro5	✓ Clean	`O=C(O)c1cccc(O)c1I`
ZINC1701211	0.593	242.2 Da LogP 2.32 TPSA 74.6	✓ Ro5	✓ Clean	`O=C(O)c1cccc(C(=O)c2ccccc2)c1O`
ZINC394382	0.593	214.2 Da LogP 2.76 TPSA 57.5	✓ Ro5	✓ Clean	`O=C(O)c1cccc(-c2ccccc2)c1O`
ZINC13547650	0.591	309.3 Da LogP -1.41 TPSA 145.6	✓ Ro5	✓ Clean	`CC(=O)OC[C@H]1O[C@@H](n2cnc3c(N)ncnc32)[C@H](O)…`
ZINC1600331	0.591	330.2 Da LogP 2.15 TPSA 149.2	✓ Ro5	✓ Clean	`O=C(O)c1cccc(C(=O)O)c1-c1c(C(=O)O)cccc1C(=O)O`
ZINC4823971	0.591	309.3 Da LogP -1.41 TPSA 145.6	✓ Ro5	✓ Clean	`CC(=O)OC[C@H]1O[C@@H](n2cnc3c(N)ncnc32)[C@@H](O…`
ZINC4823975	0.591	309.3 Da LogP -1.41 TPSA 145.6	✓ Ro5	✓ Clean	`CC(=O)OC[C@@H]1O[C@@H](n2cnc3c(N)ncnc32)[C@@H](…`
ZINC4823980	0.591	309.3 Da LogP -1.41 TPSA 145.6	✓ Ro5	✓ Clean	`CC(=O)OC[C@H]1O[C@@H](n2cnc3c(N)ncnc32)[C@@H](O…`
ZINC4823984	0.591	309.3 Da LogP -1.41 TPSA 145.6	✓ Ro5	✓ Clean	`CC(=O)OC[C@@H]1O[C@@H](n2cnc3c(N)ncnc32)[C@@H](…`
ZINC105372837	0.582	345.3 Da LogP -1.93 TPSA 197.6	✓ Ro5	✓ Clean	`Nc1ncnc2c1ncn2[C@@H]1O[C@H](COP(N)(N)=O)[C@H](O…`
ZINC13518964	0.582	347.2 Da LogP -1.86 TPSA 186.1	✓ Ro5	✓ Clean	`Nc1ncnc2c1ncn2[C@@H]1O[C@@H](COP(=O)(O)O)[C@H](…`
ZINC1532515	0.582	347.2 Da LogP -1.86 TPSA 186.1	✓ Ro5	✓ Clean	`Nc1ncnc2c1ncn2[C@H]1O[C@@H](COP(=O)(O)O)[C@H](O…`
ZINC1571045	0.582	347.2 Da LogP -1.86 TPSA 186.1	✓ Ro5	✓ Clean	`Nc1ncnc2c1ncn2[C@@H]1O[C@@H](COP(=O)(O)O)[C@@H]…`
ZINC17107643	0.582	345.3 Da LogP -1.93 TPSA 197.6	✓ Ro5	✓ Clean	`Nc1ncnc2c1ncn2[C@@H]1O[C@H](COP(N)(N)=O)[C@@H](…`
ZINC1842158	0.582	347.2 Da LogP -1.86 TPSA 186.1	✓ Ro5	✓ Clean	`Nc1ncnc2c1ncn2[C@H]1O[C@@H](COP(=O)(O)O)[C@H](O…`
ZINC204538551	0.582	345.3 Da LogP -1.93 TPSA 197.6	✓ Ro5	✓ Clean	`Nc1ncnc2c1ncn2[C@@H]1O[C@H](COP(N)(N)=O)[C@@H](…`
ZINC2046931	0.582	347.2 Da LogP -1.86 TPSA 186.1	✓ Ro5	✓ Clean	`Nc1ncnc2c1ncn2[C@@H]1O[C@@H](COP(=O)(O)O)[C@H](…`
ZINC2126310	0.582	347.2 Da LogP -1.86 TPSA 186.1	✓ Ro5	✓ Clean	`Nc1ncnc2c1ncn2[C@@H]1O[C@H](COP(=O)(O)O)[C@@H](…`
ZINC3201891	0.582	347.2 Da LogP -1.86 TPSA 186.1	✓ Ro5	✓ Clean	`Nc1ncnc2c1ncn2[C@@H]1O[C@@H](COP(=O)(O)O)[C@@H]…`
ZINC3201893	0.582	347.2 Da LogP -1.86 TPSA 186.1	✓ Ro5	✓ Clean	`Nc1ncnc2c1ncn2[C@H]1O[C@@H](COP(=O)(O)O)[C@@H](…`
ZINC3830180	0.582	347.2 Da LogP -1.86 TPSA 186.1	✓ Ro5	✓ Clean	`Nc1ncnc2c1ncn2[C@H]1O[C@@H](COP(=O)(O)O)[C@@H](…`
ZINC3860156	0.582	347.2 Da LogP -1.86 TPSA 186.1	✓ Ro5	✓ Clean	`Nc1ncnc2c1ncn2[C@@H]1O[C@H](COP(=O)(O)O)[C@@H](…`
ZINC3977897	0.582	347.2 Da LogP -1.86 TPSA 186.1	✓ Ro5	✓ Clean	`Nc1ncnc2c1ncn2[C@H]1O[C@H](COP(=O)(O)O)[C@@H](O…`
ZINC4806442	0.582	347.2 Da LogP -1.86 TPSA 186.1	✓ Ro5	✓ Clean	`Nc1ncnc2c1ncn2[C@@H]1O[C@H](COP(=O)(O)O)[C@H](O…`
ZINC8613167	0.582	347.2 Da LogP -1.86 TPSA 186.1	✓ Ro5	✓ Clean	`Nc1ncnc2c1ncn2[C@@H]1O[C@H](COP(=O)(O)O)[C@H](O…`

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.