Protein profile

PA3438

GTP cyclohydrolase I

Genome: NC_002516.2

Gene: PA3438 folE1 Structure source: AlphaFold UniProt Q9HYG8

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Amino acids 186

Annotations 8

Features 20

PDB binders 5

Druggability 0.956

Overview

Basic information about this protein and its source genome.

Accession: PA3438
Assembly: Pseudomonas aeruginosa PAO1, complete genome
Gene: PA3438 folE1
Status: annotated
Amino acids: 186
Structure source: AlphaFold

3.5.4.16

GO:0005737 The contents of a cell excluding the plasma membrane and nucleus, but including other subcellular structures. GO:0005525 Binding to GTP, guanosine triphosphate. GO:0003934 Catalysis of the reaction: GTP + H2O = 7,8-dihydroneopterin 3'-triphosphate + formate + H+. GO:0008270 Binding to a zinc ion (Zn). GO:0006730 The chemical reactions and pathways involving the transfer of one-carbon units in various oxidation states. GO:0006729 The chemical reactions and pathways resulting in the formation of tetrahydrobiopterin, the reduced form of biopterin (2-amino-4-hydroxy-6-(1,2-dihydroxypropyl)-pteridine). It functions as a hydroxylation coenzyme, e.g. in the conversion of phenylalanine to tyrosine.

Target profile

Computed evidence for target prioritization.

Human off-target: hit
Human identity (%): 57.778
Human E-value: 8.370000000000001e-79
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 0.956

Structure –

Pocket –

Sequence

Primary amino-acid sequence viewer.

Functional Annotations

Enzyme classification and Gene Ontology terms linked to this protein.

1 EC 7 GO

Enzyme Commission (EC)

3.5.4.16

Gene Ontology (GO)

GO:0005737 The contents of a cell excluding the plasma membrane and nucleus, but including other subcellular structures.
GO:0005525 Binding to GTP, guanosine triphosphate.
GO:0003934 Catalysis of the reaction: GTP + H2O = 7,8-dihydroneopterin 3'-triphosphate + formate + H+.
GO:0008270 Binding to a zinc ion (Zn).
GO:0006730 The chemical reactions and pathways involving the transfer of one-carbon units in various oxidation states.
GO:0006729 The chemical reactions and pathways resulting in the formation of tetrahydrobiopterin, the reduced form of biopterin (2-amino-4-hydroxy-6-(1,2-dihydroxypropyl)-pteridine). It functions as a hydroxylation coenzyme, e.g. in the conversion of phenylalanine to tyrosine.
GO:0046654 The chemical reactions and pathways resulting in the formation of tetrahydrofolate, 5,6,7,8-tetrahydrofolic acid, a folate derivative bearing additional hydrogens on the pterin group.

Sequence Features

Domain/signature hits from InterPro and related databases.

20 records

Show feature table

Start	End	DB	Term	Name
3	184	CDD	cd00642	GTP_cyclohydro1
1	183	Hamap	MF_00223	GTP cyclohydrolase 1 [folE].
1	183	InterPro	IPR001474	GTP cyclohydrolase I
3	183	PANTHER	PTHR11109	GTP CYCLOHYDROLASE I
3	183	InterPro	IPR001474	GTP cyclohydrolase I
62	78	ProSitePatterns	PS00859	GTP cyclohydrolase I signature 1.
62	78	InterPro	IPR018234	GTP cyclohydrolase I, conserved site
53	185	Gene3D	G3DSA:3.30.1130.10	-
53	185	InterPro	IPR043133	GTP cyclohydrolase I, C-terminal/NADPH-dependent 7-cyano-7-deazaguanine reductase
53	184	FunFam	G3DSA:3.30.1130.10:FF:000001	GTP cyclohydrolase 1
1	50	Gene3D	G3DSA:1.10.286.10	-
1	50	InterPro	IPR043134	GTP cyclohydrolase I, N-terminal domain
6	182	Pfam	PF01227	GTP cyclohydrolase I
6	182	InterPro	IPR020602	GTP cyclohydrolase I domain
1	50	FunFam	G3DSA:1.10.286.10:FF:000009	GTP cyclohydrolase 1
5	183	SUPERFAMILY	SSF55620	Tetrahydrobiopterin biosynthesis enzymes-like
110	120	ProSitePatterns	PS00860	GTP cyclohydrolase I signature 2.
110	120	InterPro	IPR018234	GTP cyclohydrolase I, conserved site
6	183	NCBIfam	TIGR00063	GTP cyclohydrolase I FolE
6	183	InterPro	IPR001474	GTP cyclohydrolase I

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 PA3438	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				0.956
1				0.443
4				0.228

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.

55 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
3PO	1WPL	P22288	258.0 Da LogP -0.69 TPSA 170.8	✓ Ro5	✓ Clean	`OP(=O)(O)OP(=O)(O)OP(=O)(O)O`
8DG	1WUR	Q5SH52	523.2 Da LogP -2.01 TPSA 298.8	3 viol.	✓ Clean	`C1[C@@H]([C@H](O[C@H]1N2C3=C(C(=O)NC(=N3)N)NC2=…`
8GT	6Z80	P30793	539.2 Da LogP -3.04 TPSA 319.1	3 viol.	✓ Clean	`C([C@@H]1[C@H]([C@H]([C@@H](O1)N2C3=C(C(=O)NC(=…`
HBI	1WPL	P22288	239.2 Da LogP -1.41 TPSA 136.6	✓ Ro5	✓ Clean	`C[C@@H]([C@@H](C1=NC2=C(NC1)N=C(NC2=O)N)O)O`
QBK	6Z88	P30793	182.2 Da LogP -0.45 TPSA 97.2	✓ Ro5	✓ Clean	`C12=NC(=O)SC1=NC(=NC2=O)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
ZINC18181336	1.000	239.2 Da LogP -1.41 TPSA 136.6	✓ Ro5	✓ Clean	`C[C@H](O)[C@H](O)C1=Nc2c(nc(N)[nH]c2=O)NC1`
ZINC6827739	1.000	258.0 Da LogP -0.69 TPSA 170.8	✓ Ro5	✓ Clean	`O=P(O)(O)OP(=O)(O)OP(=O)(O)O`
ZINC95617488	1.000	239.2 Da LogP -1.41 TPSA 136.6	✓ Ro5	✓ Clean	`C[C@@H](O)[C@@H](O)C1=Nc2c(nc(N)[nH]c2=O)NC1`
ZINC113264413	0.778	317.4 Da LogP 3.98 TPSA 63.3	✓ Ro5	✓ Clean	`N[C@@H](Cc1ccc(-c2ccc(-c3ccccc3)cc2)cc1)C(=O)O`
ZINC113264415	0.778	317.4 Da LogP 3.98 TPSA 63.3	✓ Ro5	✓ Clean	`N[C@H](Cc1ccc(-c2ccc(-c3ccccc3)cc2)cc1)C(=O)O`
ZINC2244337	0.778	241.3 Da LogP 2.31 TPSA 63.3	✓ Ro5	✓ Clean	`N[C@@H](Cc1ccc(-c2ccccc2)cc1)C(=O)O`
ZINC2244338	0.778	241.3 Da LogP 2.31 TPSA 63.3	✓ Ro5	✓ Clean	`N[C@H](Cc1ccc(-c2ccccc2)cc1)C(=O)O`
ZINC1834294	0.769	252.3 Da LogP -0.40 TPSA 126.6	✓ Ro5	✓ Clean	`N[C@@H](Cc1cccc(C[C@H](N)C(=O)O)c1)C(=O)O`
ZINC1834295	0.769	252.3 Da LogP -0.40 TPSA 126.6	✓ Ro5	✓ Clean	`N[C@@H](Cc1cccc(C[C@@H](N)C(=O)O)c1)C(=O)O`
ZINC1834297	0.769	252.3 Da LogP -0.40 TPSA 126.6	✓ Ro5	✓ Clean	`N[C@H](Cc1cccc(C[C@@H](N)C(=O)O)c1)C(=O)O`
ZINC3869856	0.744	255.2 Da LogP -2.44 TPSA 156.8	1 viol.	✓ Clean	`Nc1nc2c(c(=O)[nH]1)N=C([C@@H](O)[C@H](O)CO)CN2`
ZINC4096578	0.744	255.2 Da LogP -2.44 TPSA 156.8	1 viol.	✓ Clean	`Nc1nc2c(c(=O)[nH]1)N=C([C@H](O)[C@H](O)CO)CN2`
ZINC39351856	0.731	328.4 Da LogP 1.26 TPSA 126.6	✓ Ro5	✓ Clean	`N[C@@H](Cc1ccc(-c2ccc(C[C@H](N)C(=O)O)cc2)cc1)C…`
ZINC2561081	0.724	269.3 Da LogP 1.87 TPSA 80.4	✓ Ro5	✓ Clean	`N[C@H](Cc1ccc(C(=O)c2ccccc2)cc1)C(=O)O`
ZINC2561082	0.724	269.3 Da LogP 1.87 TPSA 80.4	✓ Ro5	✓ Clean	`N[C@@H](Cc1ccc(C(=O)c2ccccc2)cc1)C(=O)O`
ZINC12503703	0.708	427.2 Da LogP -1.42 TPSA 232.3	2 viol.	✓ Clean	`Nc1nc2c(ncn2[C@@H]2C[C@H](O)[C@@H](CO[P@@](=O)(…`
ZINC8215878	0.708	427.2 Da LogP -1.42 TPSA 232.3	2 viol.	✓ Clean	`Nc1nc2c(ncn2[C@H]2C[C@H](O)[C@@H](CO[P@@](=O)(O…`
ZINC113539705	0.700	265.3 Da LogP 2.04 TPSA 63.3	✓ Ro5	✓ Clean	`N[C@@H](Cc1ccc(C#Cc2ccccc2)cc1)C(=O)O`
ZINC113539708	0.700	265.3 Da LogP 2.04 TPSA 63.3	✓ Ro5	✓ Clean	`N[C@H](Cc1ccc(C#Cc2ccccc2)cc1)C(=O)O`
ZINC116910786	0.700	269.3 Da LogP 3.06 TPSA 88.0	✓ Ro5	Alert	`N[C@@H](Cc1ccc(/N=N/c2ccccc2)cc1)C(=O)O`
ZINC29566843	0.700	241.3 Da LogP 2.31 TPSA 63.3	✓ Ro5	✓ Clean	`N[C@H](Cc1cccc(-c2ccccc2)c1)C(=O)O`
ZINC29570997	0.700	241.3 Da LogP 2.31 TPSA 63.3	✓ Ro5	✓ Clean	`N[C@@H](Cc1cccc(-c2ccccc2)c1)C(=O)O`
ZINC44283581	0.700	257.3 Da LogP 2.43 TPSA 72.5	✓ Ro5	✓ Clean	`N[C@@H](Cc1ccc(Oc2ccccc2)cc1)C(=O)O`
ZINC44283583	0.700	257.3 Da LogP 2.43 TPSA 72.5	✓ Ro5	✓ Clean	`N[C@H](Cc1ccc(Oc2ccccc2)cc1)C(=O)O`
ZINC2111574	0.692	252.3 Da LogP -0.40 TPSA 126.6	✓ Ro5	✓ Clean	`N[C@@H](Cc1ccccc1C[C@H](N)C(=O)O)C(=O)O`
ZINC2111575	0.692	252.3 Da LogP -0.40 TPSA 126.6	✓ Ro5	✓ Clean	`N[C@@H](Cc1ccccc1C[C@@H](N)C(=O)O)C(=O)O`
ZINC2111578	0.692	252.3 Da LogP -0.40 TPSA 126.6	✓ Ro5	✓ Clean	`N[C@H](Cc1ccccc1C[C@@H](N)C(=O)O)C(=O)O`
ZINC12648269	0.690	237.3 Da LogP 0.73 TPSA 100.6	✓ Ro5	✓ Clean	`N[C@H](C[C@@H](Cc1ccccc1)C(=O)O)C(=O)O`
ZINC1616445	0.690	354.5 Da LogP 0.36 TPSA 110.2	✓ Ro5	✓ Clean	`N[C@@H](Cc1ccccc1)C(=O)NCCNC(=O)[C@H](N)Cc1cccc…`
ZINC1616446	0.690	354.5 Da LogP 0.36 TPSA 110.2	✓ Ro5	✓ Clean	`N[C@H](Cc1ccccc1)C(=O)NCCNC(=O)[C@H](N)Cc1ccccc1`
ZINC1616447	0.690	354.5 Da LogP 0.36 TPSA 110.2	✓ Ro5	✓ Clean	`N[C@@H](Cc1ccccc1)C(=O)NCCNC(=O)[C@@H](N)Cc1ccc…`
ZINC5225893	0.690	237.3 Da LogP 0.73 TPSA 100.6	✓ Ro5	✓ Clean	`N[C@@H](C[C@H](Cc1ccccc1)C(=O)O)C(=O)O`
ZINC133159	0.688	271.3 Da LogP 2.22 TPSA 72.5	✓ Ro5	✓ Clean	`N[C@@H](Cc1ccc(OCc2ccccc2)cc1)C(=O)O`
ZINC133162	0.688	271.3 Da LogP 2.22 TPSA 72.5	✓ Ro5	✓ Clean	`N[C@H](Cc1ccc(OCc2ccccc2)cc1)C(=O)O`
ZINC32333	0.679	244.1 Da LogP 1.40 TPSA 63.3	✓ Ro5	✓ Clean	`N[C@@H](Cc1ccc(Br)cc1)C(=O)O`
ZINC32334	0.679	244.1 Da LogP 1.40 TPSA 63.3	✓ Ro5	✓ Clean	`N[C@H](Cc1ccc(Br)cc1)C(=O)O`
ZINC3679925	0.679	291.1 Da LogP 1.25 TPSA 63.3	✓ Ro5	✓ Clean	`N[C@H](Cc1ccc(I)cc1)C(=O)O`
ZINC391104	0.679	291.1 Da LogP 1.25 TPSA 63.3	✓ Ro5	✓ Clean	`N[C@@H](Cc1ccc(I)cc1)C(=O)O`
ZINC4202286	0.679	209.2 Da LogP 0.34 TPSA 100.6	✓ Ro5	✓ Clean	`N[C@@H](Cc1ccc(C(=O)O)cc1)C(=O)O`
ZINC4202287	0.679	209.2 Da LogP 0.34 TPSA 100.6	✓ Ro5	✓ Clean	`N[C@H](Cc1ccc(C(=O)O)cc1)C(=O)O`
ZINC6092920	0.679	223.2 Da LogP 0.27 TPSA 100.6	✓ Ro5	✓ Clean	`N[C@@H](Cc1ccc(CC(=O)O)cc1)C(=O)O`
ZINC6506146	0.679	223.2 Da LogP 0.27 TPSA 100.6	✓ Ro5	✓ Clean	`N[C@H](Cc1ccc(CC(=O)O)cc1)C(=O)O`
ZINC6580731	0.679	225.3 Da LogP 2.44 TPSA 43.1	✓ Ro5	✓ Clean	`N[C@H](Cc1ccccc1)C(=O)c1ccccc1`
ZINC90624143	0.679	225.3 Da LogP 2.44 TPSA 43.1	✓ Ro5	✓ Clean	`N[C@@H](Cc1ccccc1)C(=O)c1ccccc1`
ZINC54918280	0.667	254.3 Da LogP 1.87 TPSA 55.1	✓ Ro5	✓ Clean	`N[C@@H](Cc1ccccc1)C(=O)NCc1ccccc1`
ZINC54918281	0.667	254.3 Da LogP 1.87 TPSA 55.1	✓ Ro5	✓ Clean	`N[C@H](Cc1ccccc1)C(=O)NCc1ccccc1`
ZINC12504289	0.662	443.2 Da LogP -2.45 TPSA 252.6	2 viol.	✓ Clean	`Nc1nc2c(ncn2[C@@H]2O[C@H](CO[P@@](=O)(O)OP(=O)(…`
ZINC35000839	0.662	443.2 Da LogP -2.45 TPSA 252.6	2 viol.	✓ Clean	`Nc1nc2c(ncn2[C@H]2O[C@@H](CO[P@@](=O)(O)OP(=O)(…`
ZINC45284491	0.662	443.2 Da LogP -2.45 TPSA 252.6	2 viol.	✓ Clean	`Nc1nc2c(ncn2[C@H]2O[C@@H](CO[P@@](=O)(O)OP(=O)(…`
ZINC8215481	0.662	443.2 Da LogP -2.45 TPSA 252.6	2 viol.	✓ Clean	`Nc1nc2c(ncn2[C@@H]2O[C@H](CO[P@@](=O)(O)OP(=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.