Protein profile

PA5338

guanosine-3',5'-bis(diphosphate) 3'-pyrophosphohydrolase

Genome: NC_002516.2

Gene: spoT PA5338 Structure source: AlphaFold UniProt Q9HTM0

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Amino acids 701

Annotations 7

Features 45

PDB binders 3

Druggability 0.637

Overview

Basic information about this protein and its source genome.

Accession: PA5338
Assembly: Pseudomonas aeruginosa PAO1, complete genome
Gene: spoT PA5338
Status: annotated
Amino acids: 701
Structure source: AlphaFold

3.1.7.2

GO:0008728 Catalysis of the reaction: ATP + GTP = AMP + guanosine 3'-diphosphate 5'-triphosphate. GO:0008893 Catalysis of the reaction: guanosine 3',5'-bis(diphosphate) + H2O = diphosphate + GDP + H+. GO:0015970 The chemical reactions and pathways resulting in the formation of guanine tetraphosphate (5'-ppGpp-3'), a derivative of guanine riboside with four phosphates. GO:0015969 The chemical reactions and pathways involving guanine tetraphosphate (5'-ppGpp-3'), a derivative of guanine riboside with four phosphates. GO:0015949 The chemical reactions and pathways by which a nucleobase, nucleoside or nucleotide small molecule is synthesized from another nucleobase, nucleoside or nucleotide small molecule. GO:0042594 Any process that results in a change in state or activity of a cell or an organism (in terms of movement, secretion, enzyme production, gene expression, etc.) as a result of a starvation stimulus, deprivation of nourishment.

Target profile

Computed evidence for target prioritization.

Human off-target: hit
Human identity (%): 32.576
Human E-value: 1.2e-09
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 0.637

Structure –

Pocket –

Sequence

Primary amino-acid sequence viewer.

Functional Annotations

Enzyme classification and Gene Ontology terms linked to this protein.

1 EC 6 GO

Enzyme Commission (EC)

3.1.7.2

Gene Ontology (GO)

GO:0008728 Catalysis of the reaction: ATP + GTP = AMP + guanosine 3'-diphosphate 5'-triphosphate.
GO:0008893 Catalysis of the reaction: guanosine 3',5'-bis(diphosphate) + H2O = diphosphate + GDP + H+.
GO:0015970 The chemical reactions and pathways resulting in the formation of guanine tetraphosphate (5'-ppGpp-3'), a derivative of guanine riboside with four phosphates.
GO:0015969 The chemical reactions and pathways involving guanine tetraphosphate (5'-ppGpp-3'), a derivative of guanine riboside with four phosphates.
GO:0015949 The chemical reactions and pathways by which a nucleobase, nucleoside or nucleotide small molecule is synthesized from another nucleobase, nucleoside or nucleotide small molecule.
GO:0042594 Any process that results in a change in state or activity of a cell or an organism (in terms of movement, secretion, enzyme production, gene expression, etc.) as a result of a starvation stimulus, deprivation of nourishment.

Sequence Features

Domain/signature hits from InterPro and related databases.

45 records

Show feature table

Start	End	DB	Term	Name
26	697	NCBIfam	TIGR00691	RelA/SpoT family protein
26	697	InterPro	IPR004811	RelA/SpoT family
3	190	Gene3D	G3DSA:1.10.3210.10	Hypothetical protein af1432
386	447	ProSiteProfiles	PS51880	TGS domain profile.
386	447	InterPro	IPR004095	TGS
622	701	FunFam	G3DSA:3.30.70.260:FF:000027	(P)ppGpp synthetase II
628	698	CDD	cd04876	ACT_RelA-SpoT
389	447	CDD	cd01668	TGS_RSH
389	447	InterPro	IPR033655	RelA/SpoT, TGS domain
622	701	Gene3D	G3DSA:3.30.70.260	-
459	548	Pfam	PF19296	RelA/SpoT, AH and RIS domains
459	548	InterPro	IPR045600	RelA/SpoT, AH and RIS domains
26	175	Pfam	PF13328	HD domain
381	454	Gene3D	G3DSA:3.10.20.30	-
381	454	InterPro	IPR012675	Beta-grasp domain superfamily
192	325	FunFam	G3DSA:3.30.460.10:FF:000001	GTP pyrophosphokinase RelA
622	698	Pfam	PF13291	ACT domain
622	698	InterPro	IPR002912	ACT domain
375	447	SUPERFAMILY	SSF81271	TGS-like
375	447	InterPro	IPR012676	TGS-like
4	191	FunFam	G3DSA:1.10.3210.10:FF:000001	GTP pyrophosphokinase RelA
8	698	PANTHER	PTHR21262	GUANOSINE-3',5'-BIS DIPHOSPHATE 3'-PYROPHOSPHOHYDROLASE
235	345	SMART	SM00954	RelA_SpoT_2
235	345	InterPro	IPR007685	RelA/SpoT
380	454	FunFam	G3DSA:3.10.20.30:FF:000002	GTP pyrophosphokinase (RelA/SpoT)
43	166	CDD	cd00077	HDc
43	166	InterPro	IPR003607	HD/PDEase domain
627	701	ProSiteProfiles	PS51671	ACT domain profile.
627	701	InterPro	IPR002912	ACT domain
388	447	Pfam	PF02824	TGS domain
388	447	InterPro	IPR004095	TGS
215	331	CDD	cd05399	NT_Rel-Spo_like
215	331	InterPro	IPR007685	RelA/SpoT
41	153	SMART	SM00471	hd_13
41	153	InterPro	IPR003607	HD/PDEase domain
235	345	Pfam	PF04607	Region found in RelA / SpoT proteins
45	144	ProSiteProfiles	PS51831	HD domain profile.
45	144	InterPro	IPR006674	HD domain
5	191	SUPERFAMILY	SSF109604	HD-domain/PDEase-like
181	392	SUPERFAMILY	SSF81301	Nucleotidyltransferase
181	392	InterPro	IPR043519	Nucleotidyltransferase superfamily
195	325	Gene3D	G3DSA:3.30.460.10	Beta Polymerase, domain 2
195	325	InterPro	IPR043519	Nucleotidyltransferase superfamily
624	699	SUPERFAMILY	SSF55021	ACT-like
624	699	InterPro	IPR045865	ACT-like domain

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

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 PA5338	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				0.637
5				0.247

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.

60 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
G4P	6S2T	Q5SHL3	603.2 Da LogP -2.22 TPSA 345.6	3 viol.	✓ Clean	`c1nc2c(n1[C@H]3[C@@H]([C@@H]([C@H](O3)CO[P@](=O…`
GN3	6S2U	Q5SHL3	602.2 Da LogP -2.65 TPSA 348.4	3 viol.	✓ Clean	`c1nc2c(n1[C@H]3[C@@H]([C@@H]([C@H](O3)COP(=O)(O…`
GPX	1VJ7	Q54089	505.2 Da LogP -1.29 TPSA 267.9	3 viol.	✓ Clean	`c1nc2c(n1[C@H]3[C@H]4[C@@H]([C@H](O3)CO[P@](=O)…`

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).

Ligand	UniProt (homolog)	pchembl	MW · LogP · TPSA	Lipinski	PAINS	SMILES
CHEMBL1163519	P0AG20	—	425.2 Da LogP -1.31 TPSA 223.1	1 viol.	✓ Clean	`Nc1nc2c(ncn2[C@H]2C[C@H](OP(=O)(O)CP(=O)(O)O)[C…`
CHEMBL1163520	Q54089	—	669.3 Da LogP -0.98 TPSA 330.2	3 viol.	✓ Clean	`CC(C)C(=O)Nc1nc2c(ncn2[C@@H]2O[C@H](COP(=O)(O)C…`
CHEMBL1163568	Q54089	—	599.2 Da LogP -2.00 TPSA 327.2	3 viol.	✓ Clean	`Nc1nc2c(ncn2[C@@H]2O[C@H](COP(=O)(O)CP(=O)(O)O)…`
CHEMBL1163576	Q54089	—	583.2 Da LogP -0.97 TPSA 306.9	3 viol.	✓ Clean	`Nc1nc2c(ncn2[C@H]2C[C@H](OP(=O)(O)CP(=O)(O)O)[C…`
CHEMBL1163621	Q54089	—	481.3 Da LogP -0.54 TPSA 221.3	1 viol.	✓ Clean	`CC1(C)O[C@@H]2[C@H](O1)[C@@H](COP(=O)(O)CP(=O)(…`
CHEMBL1164398	Q54089	—	783.6 Da LogP 2.04 TPSA 319.2	3 viol.	✓ Clean	`CC(C)C(=O)Nc1nc2c(ncn2[C@@H]2O[C@H](COP(=O)(O)C…`
GP2	Q54089	—	441.2 Da LogP -2.34 TPSA 243.3	2 viol.	✓ Clean	`c1nc2c(n1[C@H]3[C@@H]([C@@H]([C@H](O3)CO[P@](=O…`

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
ZINC4543679	0.862	347.2 Da LogP -1.54 TPSA 185.8	✓ Ro5	✓ Clean	`Nc1nc2c(ncn2[C@@H]2C[C@H](OP(=O)(O)O)[C@H](CO)O…`
ZINC104869865	0.836	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)(O…`
ZINC12504289	0.836	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)(…`
ZINC34541308	0.836	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	0.836	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	0.836	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)(…`
ZINC80639694	0.836	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	0.836	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)(…`
ZINC12503703	0.738	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	0.738	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…`
ZINC12503440	0.719	363.2 Da LogP -2.57 TPSA 206.0	1 viol.	✓ Clean	`Nc1nc2c(ncn2[C@@H]2O[C@H](CO)[C@@H](OP(=O)(O)O)…`
ZINC1530370	0.719	363.2 Da LogP -2.57 TPSA 206.0	1 viol.	✓ Clean	`Nc1nc2c(ncn2[C@H]2O[C@@H](CO)[C@H](OP(=O)(O)O)[…`
ZINC28631009	0.719	363.2 Da LogP -2.57 TPSA 206.0	1 viol.	✓ Clean	`Nc1nc2c(ncn2[C@@H]2O[C@H](CO)[C@H](OP(=O)(O)O)[…`
ZINC3872740	0.719	363.2 Da LogP -2.57 TPSA 206.0	1 viol.	✓ Clean	`Nc1nc2c(ncn2[C@H]2O[C@@H](CO)[C@@H](OP(=O)(O)O)…`
ZINC3872741	0.719	363.2 Da LogP -2.57 TPSA 206.0	1 viol.	✓ Clean	`Nc1nc2c(ncn2[C@@H]2O[C@@H](CO)[C@@H](OP(=O)(O)O…`
ZINC3872742	0.719	363.2 Da LogP -2.57 TPSA 206.0	1 viol.	✓ Clean	`Nc1nc2c(ncn2[C@H]2O[C@@H](CO)[C@@H](OP(=O)(O)O)…`
ZINC3872743	0.719	363.2 Da LogP -2.57 TPSA 206.0	1 viol.	✓ Clean	`Nc1nc2c(ncn2[C@@H]2O[C@@H](CO)[C@@H](OP(=O)(O)O…`
ZINC12501413	0.714	363.2 Da LogP -2.57 TPSA 206.0	1 viol.	✓ Clean	`Nc1nc2c(ncn2[C@@H]2O[C@H](COP(=O)(O)O)[C@@H](O)…`
ZINC12958448	0.714	363.2 Da LogP -2.57 TPSA 206.0	1 viol.	✓ Clean	`Nc1nc2c(ncn2[C@@H]2O[C@H](COP(=O)(O)O)[C@H](O)[…`
ZINC1532555	0.714	363.2 Da LogP -2.57 TPSA 206.0	1 viol.	✓ Clean	`Nc1nc2c(ncn2[C@H]2O[C@@H](COP(=O)(O)O)[C@H](O)[…`
ZINC16546189	0.714	363.2 Da LogP -2.57 TPSA 206.0	1 viol.	✓ Clean	`Nc1nc2c(ncn2[C@@H]2O[C@H](COP(=O)(O)O)[C@H](O)[…`
ZINC2159505	0.714	363.2 Da LogP -2.57 TPSA 206.0	1 viol.	✓ Clean	`Nc1nc2c(ncn2[C@@H]2O[C@H](COP(=O)(O)O)[C@@H](O)…`
ZINC3073318	0.714	363.2 Da LogP -2.57 TPSA 206.0	1 viol.	✓ Clean	`Nc1nc2c(ncn2[C@H]2O[C@@H](COP(=O)(O)O)[C@@H](O)…`
ZINC3869963	0.714	363.2 Da LogP -2.57 TPSA 206.0	1 viol.	✓ Clean	`Nc1nc2c(ncn2[C@H]2O[C@@H](COP(=O)(O)O)[C@@H](O)…`
ZINC3869965	0.714	363.2 Da LogP -2.57 TPSA 206.0	1 viol.	✓ Clean	`Nc1nc2c(ncn2[C@@H]2O[C@@H](COP(=O)(O)O)[C@@H](O…`
ZINC9334496	0.714	363.2 Da LogP -2.57 TPSA 206.0	1 viol.	✓ Clean	`Nc1nc2c(ncn2[C@H]2O[C@@H](COP(=O)(O)O)[C@H](O)[…`
ZINC12501360	0.657	363.2 Da LogP -2.57 TPSA 206.0	1 viol.	✓ Clean	`Nc1nc2c(ncn2[C@@H]2O[C@H](CO)[C@@H](O)[C@@H]2OP…`
ZINC100058967	0.632	443.2 Da LogP -2.45 TPSA 252.6	2 viol.	✓ Clean	`Nc1nc(=O)c2ncn([C@H]3O[C@H](CO[P@](=O)(O)OP(=O)…`
ZINC12504287	0.632	443.2 Da LogP -2.45 TPSA 252.6	2 viol.	✓ Clean	`Nc1nc(=O)c2ncn([C@@H]3O[C@@H](CO[P@@](=O)(O)OP(…`
ZINC12504288	0.632	443.2 Da LogP -2.45 TPSA 252.6	2 viol.	✓ Clean	`Nc1nc(=O)c2ncn([C@H]3O[C@@H](CO[P@@](=O)(O)OP(=…`
ZINC31308647	0.632	443.2 Da LogP -2.45 TPSA 252.6	2 viol.	✓ Clean	`Nc1nc(=O)c2ncn([C@@H]3O[C@@H](CO[P@@](=O)(O)OP(…`
ZINC106686432	0.627	428.2 Da LogP -2.03 TPSA 226.5	2 viol.	✓ Clean	`O=c1[nH]cnc2c1ncn2[C@H]1O[C@@H](CO[P@](=O)(O)OP…`
ZINC12296728	0.627	347.2 Da LogP -1.54 TPSA 185.8	✓ Ro5	✓ Clean	`Nc1nc2c(ncn2[C@H]2C[C@@H](O)[C@@H](COP(=O)(O)O)…`
ZINC12958393	0.627	428.2 Da LogP -2.03 TPSA 226.5	2 viol.	✓ Clean	`O=c1[nH]cnc2c1ncn2[C@@H]1O[C@@H](CO[P@](=O)(O)O…`
ZINC13527599	0.627	347.2 Da LogP -1.54 TPSA 185.8	✓ Ro5	✓ Clean	`Nc1nc2c(ncn2[C@@H]2C[C@@H](O)[C@@H](COP(=O)(O)O…`
ZINC13527603	0.627	347.2 Da LogP -1.54 TPSA 185.8	✓ Ro5	✓ Clean	`Nc1nc2c(ncn2[C@@H]2C[C@H](O)[C@@H](COP(=O)(O)O)…`
ZINC1532627	0.627	347.2 Da LogP -1.54 TPSA 185.8	✓ Ro5	✓ Clean	`Nc1nc2c(ncn2[C@@H]2C[C@@H](O)[C@H](COP(=O)(O)O)…`
ZINC1730395	0.627	347.2 Da LogP -1.54 TPSA 185.8	✓ Ro5	✓ Clean	`Nc1nc2c(ncn2[C@H]2C[C@H](O)[C@@H](COP(=O)(O)O)O…`
ZINC35024781	0.627	428.2 Da LogP -2.03 TPSA 226.5	2 viol.	✓ Clean	`O=c1[nH]cnc2c1ncn2[C@H]1O[C@@H](CO[P@@](=O)(O)O…`
ZINC35024785	0.627	428.2 Da LogP -2.03 TPSA 226.5	2 viol.	✓ Clean	`O=c1[nH]cnc2c1ncn2[C@H]1O[C@@H](CO[P@@](=O)(O)O…`
ZINC35024786	0.627	428.2 Da LogP -2.03 TPSA 226.5	2 viol.	✓ Clean	`O=c1[nH]cnc2c1ncn2[C@@H]1O[C@@H](CO[P@@](=O)(O)…`
ZINC3869846	0.627	347.2 Da LogP -1.54 TPSA 185.8	✓ Ro5	✓ Clean	`Nc1nc2c(ncn2[C@@H]2C[C@H](O)[C@H](COP(=O)(O)O)O…`
ZINC3869847	0.627	347.2 Da LogP -1.54 TPSA 185.8	✓ Ro5	✓ Clean	`Nc1nc2c(ncn2[C@H]2C[C@H](O)[C@H](COP(=O)(O)O)O2…`
ZINC3869848	0.627	347.2 Da LogP -1.54 TPSA 185.8	✓ Ro5	✓ Clean	`Nc1nc2c(ncn2[C@H]2C[C@@H](O)[C@H](COP(=O)(O)O)O…`
ZINC4261903	0.627	428.2 Da LogP -2.03 TPSA 226.5	2 viol.	✓ Clean	`O=c1[nH]cnc2c1ncn2[C@@H]1O[C@H](CO[P@@](=O)(O)O…`
ZINC80601236	0.627	428.2 Da LogP -2.03 TPSA 226.5	2 viol.	✓ Clean	`O=c1[nH]cnc2c1ncn2[C@@H]1O[C@H](CO[P@@](=O)(O)O…`
ZINC95921560	0.627	428.2 Da LogP -2.03 TPSA 226.5	2 viol.	✓ Clean	`O=c1[nH]cnc2c1ncn2[C@H]1O[C@@H](CO[P@@](=O)(O)O…`
ZINC71774763	0.625	432.3 Da LogP -2.23 TPSA 198.3	1 viol.	✓ Clean	`Nc1nc2c(ncn2[C@@H]2O[C@H](CO[P@](=O)(O)N3CCOCC3…`
ZINC100727895	0.621	347.2 Da LogP -2.50 TPSA 196.8	1 viol.	✓ Clean	`Nc1nc2c(ncn2[C@@H]2O[C@H](CO)[C@@H](O)[C@H]2P(=…`
ZINC17610743	0.621	347.2 Da LogP -2.50 TPSA 196.8	1 viol.	✓ Clean	`Nc1nc2c(ncn2[C@@H]2O[C@H](CO)[C@@H](O)[C@@H]2P(…`

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.