Target Pathogen

Overview

Basic information about this protein and its source genome.

Accession: PA4557
Assembly: Pseudomonas aeruginosa PAO1, complete genome
Gene: ispH lytB PA4557
Status: annotated
Amino acids: 314
Structure source: AlphaFold

EC

1.17.7.4

GO

GO:0005829 The part of the cytoplasm that does not contain organelles but which does contain other particulate matter, such as protein complexes. 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:0051745 Catalyzes the conversion of (2E)-4-hydroxy-3-methylbut-2-enyl diphosphate + 2 H+ + 2 reduced [2Fe-2S]-[ferredoxin] to isopentenyl diphosphate (IPP) and dimethylallyl diphosphate (DMAPP) releasing H2O + 2 oxidized [2Fe-2S]-[ferredoxin]. Note that (E)-4-hydroxy-3-methylbut-2-en-1-yl diphosphate is an alternative name for 1-hydroxy-2-methyl-2-(E)-butenyl 4-diphosphate. GO:0046872 Binding to a metal ion. GO:0050992 The chemical reactions and pathways resulting in the formation of dimethylallyl diphosphate. GO:0019288 The chemical reactions and pathways resulting in the formation of isopentenyl diphosphate by the mevalonate-independent pathway. Isopentenyl diphosphate (IPP) is the fundamental unit in isoprenoid biosynthesis and is biosynthesized from pyruvate and glyceraldehyde 3-phosphate via intermediates, including 1-deoxy-D-xylulose 5-phosphate.

Target profile

Computed evidence for target prioritization.

Human off-target: No hit
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 0.584

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)

1

1.17.7.4

Gene Ontology (GO)

7

GO:0005829 The part of the cytoplasm that does not contain organelles but which does contain other particulate matter, such as protein complexes.
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:0051745 Catalyzes the conversion of (2E)-4-hydroxy-3-methylbut-2-enyl diphosphate + 2 H+ + 2 reduced [2Fe-2S]-[ferredoxin] to isopentenyl diphosphate (IPP) and dimethylallyl diphosphate (DMAPP) releasing H2O + 2 oxidized [2Fe-2S]-[ferredoxin]. Note that (E)-4-hydroxy-3-methylbut-2-en-1-yl diphosphate is an alternative name for 1-hydroxy-2-methyl-2-(E)-butenyl 4-diphosphate.
GO:0046872 Binding to a metal ion.
GO:0050992 The chemical reactions and pathways resulting in the formation of dimethylallyl diphosphate.
GO:0019288 The chemical reactions and pathways resulting in the formation of isopentenyl diphosphate by the mevalonate-independent pathway. Isopentenyl diphosphate (IPP) is the fundamental unit in isoprenoid biosynthesis and is biosynthesized from pyruvate and glyceraldehyde 3-phosphate via intermediates, including 1-deoxy-D-xylulose 5-phosphate.
GO:0016114 The chemical reactions and pathways resulting in the formation of terpenoids, any member of a class of compounds characterized by an isoprenoid chemical structure.

Sequence Features

Domain/signature hits from InterPro and related databases.

12 records

Show feature table

Start	End	DB	Term	Name
3	283	CDD	cd13944	lytB_ispH
3	283	InterPro	IPR003451	4-hydroxy-3-methylbut-2-enyl diphosphate reductase
1	311	PANTHER	PTHR30426	4-HYDROXY-3-METHYLBUT-2-ENYL DIPHOSPHATE REDUCTASE
1	311	InterPro	IPR003451	4-hydroxy-3-methylbut-2-enyl diphosphate reductase
12	96	Gene3D	G3DSA:3.40.50.11270	-
97	197	Gene3D	G3DSA:3.40.1010.20	-
5	282	Gene3D	G3DSA:3.40.1010.20	-
3	283	Pfam	PF02401	LytB protein
2	285	NCBIfam	TIGR00216	4-hydroxy-3-methylbut-2-enyl diphosphate reductase
2	285	InterPro	IPR003451	4-hydroxy-3-methylbut-2-enyl diphosphate reductase
1	287	Hamap	MF_00191	4-hydroxy-3-methylbut-2-enyl diphosphate reductase [ispH].
1	287	InterPro	IPR003451	4-hydroxy-3-methylbut-2-enyl diphosphate reductase

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 PA4557	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				0.584
4				0.272

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.

30 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
0CG	3URK	P62623	216.0 Da LogP -0.15 TPSA 113.3	✓ Ro5	✓ Clean	`C#CCOP(=O)(O)OP(=O)(O)O`
0CH	3UV6	P62623	250.1 Da LogP -0.01 TPSA 133.5	✓ Ro5	✓ Clean	`C(CCOP(=O)(O)OP(=O)(O)O)CO`
0CJ	3UTD	P62623	262.1 Da LogP 0.58 TPSA 130.4	✓ Ro5	✓ Clean	`CC(=O)CCCOP(=O)(O)OP(=O)(O)O`
0CM	3UV3	P62623	230.0 Da LogP 0.24 TPSA 113.3	✓ Ro5	✓ Clean	`CC#CCOP(=O)(O)OP(=O)(O)O`
0CN	3UV7	P62623	230.0 Da LogP 0.55 TPSA 113.3	✓ Ro5	✓ Clean	`C=C=CCOP(=O)(O)OP(=O)(O)O`
0JX	3UTC	P62623	248.1 Da LogP 0.67 TPSA 133.5	✓ Ro5	✓ Clean	`C(COP(=O)(O)OP(=O)(O)O)/C=C/O`
0K2	3UWM	P62623	248.1 Da LogP 0.19 TPSA 130.4	✓ Ro5	✓ Clean	`C(CC=O)COP(=O)(O)OP(=O)(O)O`
0O3	4EB3	P62623	262.1 Da LogP 0.15 TPSA 133.5	✓ Ro5	✓ Clean	`C=C(CCOP(=O)(O)OP(=O)(O)O)CO`
10D	4H4C	P62623	264.1 Da LogP 1.13 TPSA 113.3	✓ Ro5	✓ Clean	`C/C(=C\COP(=O)(O)OP(=O)(O)O)/CF`
10E	3ZGL	P62623	261.1 Da LogP 0.12 TPSA 139.3	✓ Ro5	✓ Clean	`C/C(=C\COP(=O)(O)OP(=O)(O)O)/CN`
10G	3ZGN	P62623	278.2 Da LogP 1.09 TPSA 113.3	✓ Ro5	✓ Clean	`C/C(=C\COP(=O)(O)OP(=O)(O)O)/CS`
DMA	3KEF	P62623	246.1 Da LogP 1.18 TPSA 113.3	✓ Ro5	✓ Clean	`CC(=CCO[P@@](=O)(O)OP(=O)(O)O)C`
EIP	3KE8	P62623	264.1 Da LogP 0.23 TPSA 133.5	✓ Ro5	✓ Clean	`C[C@@H](CCO[P@](=O)(O)OP(=O)(O)O)CO`
F3S	3F7T	P62623	295.8 Da LogP 2.59 TPSA 0.0	✓ Ro5	✓ Clean	`S1[Fe]2S[Fe]3[S]2[Fe]1S3`
H6P	3T0F	P62623	262.1 Da LogP 0.15 TPSA 133.5	✓ Ro5	✓ Clean	`C/C(=C\CO[P@@](=O)(O)OP(=O)(O)O)/CO`
IPE	3KEM	P62623	246.1 Da LogP 1.18 TPSA 113.3	✓ Ro5	✓ Clean	`CC(=C)CCO[P@@](=O)(O)OP(=O)(O)O`
POP	3F7T	P62623	176.0 Da LogP -2.08 TPSA 129.9	✓ Ro5	✓ Clean	`O[P@@](=O)([O-])O[P@@](=O)(O)[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
43W	O67625	7.22	230.0 Da LogP 0.24 TPSA 113.3	✓ Ro5	✓ Clean	`C#CCCOP(=O)(O)OP(=O)(O)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
ZINC8215654	1.000	246.1 Da LogP 1.18 TPSA 113.3	✓ Ro5	✓ Clean	`C=C(C)CCO[P@@](=O)(O)OP(=O)(O)O`
ZINC71769106	0.923	326.1 Da LogP 1.30 TPSA 159.8	✓ Ro5	✓ Clean	`CC(C)=CCO[P@@](=O)(O)O[P@@](=O)(O)OP(=O)(O)O`
ZINC8215849	0.719	314.2 Da LogP 2.91 TPSA 113.3	✓ Ro5	✓ Clean	`CC(C)=CCC/C(C)=C/CO[P@@](=O)(O)OP(=O)(O)O`
ZINC12494625	0.697	382.3 Da LogP 4.63 TPSA 113.3	✓ Ro5	✓ Clean	`CC(C)=CCC/C(C)=C/CC/C(C)=C/CO[P@@](=O)(O)OP(=O)…`
ZINC2356589248	0.697	382.3 Da LogP 4.63 TPSA 113.3	✓ Ro5	✓ Clean	`CC(C)=CCCC(C)=CCCC(C)=CCO[P@](=O)(O)OP(=O)(O)O`
ZINC34661063	0.676	394.2 Da LogP 3.02 TPSA 159.8	✓ Ro5	✓ Clean	`CC(C)=CCC/C(C)=C/CO[P@@](=O)(O)O[P@@](=O)(O)OP(…`
ZINC8218174	0.657	462.3 Da LogP 4.75 TPSA 159.8	✓ Ro5	✓ Clean	`CC(C)=CCC/C(C)=C/CC/C(C)=C/CO[P@@](=O)(O)O[P@@]…`
ZINC34020319	0.588	260.1 Da LogP 0.61 TPSA 124.3	✓ Ro5	✓ Clean	`C/C(=C\CC[P@@](=O)(O)OP(=O)(O)O)CO`
ZINC13539354	0.571	332.2 Da LogP 3.20 TPSA 113.3	✓ Ro5	✓ Clean	`CC(C)=CCC/C(C)=C(\F)CO[P@](=O)(O)OP(=O)(O)O`
ZINC39419974	0.520	212.1 Da LogP 1.04 TPSA 44.8	✓ Ro5	✓ Clean	`C#CCOP(=O)(OCC#C)OCC#C`
ZINC1532829	0.500	234.2 Da LogP 2.79 TPSA 66.8	✓ Ro5	✓ Clean	`CC(C)=CCC/C(C)=C/COP(=O)(O)O`
ZINC2579357	0.500	248.1 Da LogP 1.26 TPSA 113.3	✓ Ro5	✓ Clean	`CC(C)CCO[P@](=O)(O)OP(=O)(O)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.

PA4557