KpATCC43816 Protein target profile

4-hydroxy-3-methylbut-2-enyl diphosphate reductase

Accession: VK055_2551

Gene: ispH AIK81148.1 3D evidence: AlphaFold DB model + ColabFold model Metabolism 2 reactions UniProt A0A0H3GN13

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Length 316

Pocket druggability (P2Rank · AlphaFold DB model) 0.806

Metabolic reactions 2

Chokepoint No

Direct ligand evidence 0 32 total records

Functional annotation 1 EC 7 GO

Target summary

Strong target candidate with converging metabolic, structural and chemical evidence.

Automated synthesis of the evidence currently loaded. Review the underlying records before prioritizing this protein.

Main supporting evidence

Independent pocket support: P2Rank + FPocket Both predictors report a high-scoring binding site (P2Rank 0.81, FPocket 0.75). Use the 3D pocket comparison to verify whether they identify the same site. Central metabolic position More central than 94.1% of genes in this genome. No isoenzyme backup detected Imported GPR rules do not show an alternative enzyme for the catalyzed reaction set. No similar human protein detected The current BLAST sequence screen did not find a significant human match, lowering apparent off-target risk. Review the complete evidence below

Risks to review

Evidence coverage

Core evidence streams are available for this target.

Terms and data sources used on this page

PDB: experimentally determined structures from the Protein Data Bank. These are the strongest structural evidence, but may cover only part of the protein.

AlphaFold DB model: a precomputed predicted structure downloaded from AlphaFold Database/UniProt, not an experiment performed here.

ColabFold model: a predicted structure generated for this workspace; interpret it with coverage and confidence.

pLDDT: confidence score for predicted structures. High values support local geometry; low values mean the region should not drive pocket interpretation.

FPocket / P2Rank: software tools that predict possible ligand-binding pockets on a 3D structure. They are useful screening signals, not experimental validation.

Druggability: a pocket-based estimate of whether a small molecule could bind productively. It does not mean a drug already exists.

PDB ligand: a compound observed in an experimental structure. Direct same-protein records are stronger than homolog-transferred records.

ChEMBL: a public database of measured compound bioactivity. Direct entries are stronger than entries transferred from similar proteins.

ZINC: a purchasable-compound database. Here it marks proposed candidates from chemical similarity, not measured binders.

LigQ / LigQ_2: an internal Target pipeline step that gathers PDB, ChEMBL, and ZINC ligand evidence for each protein.

Off-target: sequence similarity to proteins we prefer not to hit, such as human proteins or beneficial gut microbiome proteins.

DEG: Database of Essential Genes. A match suggests the protein resembles genes known to be essential in other organisms.

Roary / CoreCruncher: pan-genome tools used to decide whether a gene is core across analyzed strains or accessory/strain-specific.

EC / GO: functional annotations: EC describes enzyme reactions; GO describes biological process, molecular function, or cellular component.

KEGG pathway: a curated metabolic route label used here to group reactions imported from the metabolic model.

Chokepoint: a metabolic reaction that is the only producer or consumer of a metabolite in the imported model.

Prioritization evidence

Selectivity, essentiality, structural confidence, conservation, and predicted binding-site evidence.

Off-target risk

Human off-target: No hit
Gut microbiome similarity: 7.4% of screened genomes Lower prevalence suggests narrower overlap with the screened gut microbiome.

Essentiality

Essential (DEG): Y
DEG identity (%): 93.671 Higher values support similarity to known essential genes.
DEG E-value: 0.0 Smaller values mean stronger essential-gene similarity.

Structure confidence

ColabFold pLDDT: 97.25 0-100 confidence; >70 supports local structural interpretation.

Binding-site evidence

AlphaFold DB / UniProt model

P2Rank's binding-site probability is the primary druggability signal shown across the app; FPocket's druggability score is shown alongside it for comparison. Both estimate small-molecule pocket quality after applying the curated structure priority — neither is experimental binding evidence. The 3D viewer may show a different loaded structure, so visible pockets can differ.

Druggability (P2Rank) 0.806

Structure A0A0H3GN13

Pocket Pocket 1

Druggability (FPocket) 0.749

Structure A0A0H3GN13

Pocket Pocket 2

ColabFold model

P2Rank 0.831 · Pocket 1

FPocket 0.738 · Pocket 4

Core conservation Conserved core gene

Roary core

CoreCruncher core

Gut microbiome 353 / 4744 genomes with a hit

Prevalence 7.4%

Metabolic context

Reactions catalyzed, pathway membership, and centrality in the genome-scale metabolic network.

Explore metabolic network

Metabolic context: more central than 94.1% of genes in this genome, no human homolog detected.

Relative network centrality 94.1% more central than 94.1% of genes in this genome

Chokepoint Not a chokepoint

Imported from KpATCC43816.sbml · 2026-07-09

Sequence

Primary amino-acid sequence viewer.

MQILLANPRGFCAGVDRAISIVENALTLYGAPIYVRHEVVHNRYVVDSLRKRGAIFIEQISEVPDGAILIFSAHGVSQAVRNEAKSRDLTVFDATCPLVTKVHMEVARASRRGEESILIGHAGHPEVEGTMGQYNNPQGGMYLVESPEDVLKLEVKNDARLSFMTQTTLSVDDTSDVIDALRARFPKIVGPRKDDICYATTNRQEAVRALAEQADVVLVVGSKNSSNSNRLAELAQRMGKAAYLIDDASDIQEAWVKDAACVGVTAGASAPDILVQNVITRLQELGGGEAVPLEGREENIVFEVPKELRVDVREVE

Functional annotations

Enzyme classification and Gene Ontology terms linked to this protein.

1 EC 7 GO

Subcellular localization

Localization: Cytoplasmic

Enzyme Commission (EC)

1.17.7.4

Gene Ontology (GO)

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: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:0046872 Binding to a metal ion.
GO:0005737 The contents of a cell excluding the plasma membrane and nucleus, but including other subcellular structures.
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: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 domains and features

Domain and signature matches imported from InterPro and related databases.

13 records

Show feature table

Start	End	DB	Term	Name
12	96	FunFam	G3DSA:3.40.50.11270:FF:000001	4-hydroxy-3-methylbut-2-enyl diphosphate reductase
1	314	PANTHER	PTHR30426	4-HYDROXY-3-METHYLBUT-2-ENYL DIPHOSPHATE REDUCTASE
1	314	InterPro	IPR003451	4-hydroxy-3-methylbut-2-enyl diphosphate reductase
2	284	NCBIfam	TIGR00216	4-hydroxy-3-methylbut-2-enyl diphosphate reductase
2	284	InterPro	IPR003451	4-hydroxy-3-methylbut-2-enyl diphosphate reductase
1	286	Hamap	MF_00191	4-hydroxy-3-methylbut-2-enyl diphosphate reductase [ispH].
1	286	InterPro	IPR003451	4-hydroxy-3-methylbut-2-enyl diphosphate reductase
97	196	Gene3D	G3DSA:3.40.1010.20	-
12	96	Gene3D	G3DSA:3.40.50.11270	-
3	282	CDD	cd13944	lytB_ispH
3	282	InterPro	IPR003451	4-hydroxy-3-methylbut-2-enyl diphosphate reductase
3	282	Pfam	PF02401	LytB protein
5	281	Gene3D	G3DSA:3.40.1010.20	-

3D structure

Selected loaded structure. Experimental PDB entries may cover only a portion of the sequence; AlphaFold DB and ColabFold models typically cover the full protein but remain computational predictions.

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Pocket score High Medium Low

How colors and pocket overlays are used

Uniform protein color marks the displayed model as a single molecular object.

Experimental PDB structures may be colored by chain to distinguish subunits or copies present in the file.

Pocket colors and alpha spheres are evidence overlays for predicted binding cavities; they are not alternative protein chains.

'Alpha spheres' is FPocket's own cavity-shape geometry, imported when available and aligned with the loaded structure.

'Pocket atoms'/'Predicted site atoms' show the pocket's residue atoms instead: P2Rank reports residues rather than alpha spheres, and FPocket falls back to this when alpha-sphere geometry is unavailable or doesn't align.

'No pocket geometry' means neither alpha spheres nor residue-position data could be found for that pocket; the layer just highlights the same residues as 'Nearby residues'.

Pocket details Inspect a specific pocket, or open the full viewer

Binding pockets · P2Rank

Druggability (P2Rank): high ≥ 0.5 · medium 0.2–0.49 · low < 0.2

Pocket 1 P2Rank #1

0.806

Likely same site as FPocket 2 0.9 Å 18 shared residues 90% of smaller site

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Surrounding area

Pocket 2 P2Rank #2

0.019

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Surrounding area

Pocket 3 P2Rank #3

0.018

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Surrounding area

Pocket 4 P2Rank #4

0.013

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Surrounding area

Pocket 5 P2Rank #5

0.013

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Surrounding area

Binding pockets · FPocket

Druggability (FPocket): high ≥ 0.7 · medium 0.4–0.69 · low < 0.4

Pocket 1 FPocket #2

0.749

Likely same site as P2Rank 1 0.9 Å 18 shared residues 90% of smaller site

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Surrounding area

Residue sets

UniProt: Active site:126-126 Proton donor

UniProt: Binding site:12-12

UniProt: Binding site:124-124

UniProt: Binding site:167-167

UniProt: Binding site:197-197

UniProt: Binding site:225-225

UniProt: Binding site:226-226

UniProt: Binding site:227-227

UniProt: Binding site:269-269

UniProt: Binding site:41-41

UniProt: Binding site:74-74

UniProt: Binding site:96-96

Binding pockets · P2Rank

Druggability (P2Rank): high ≥ 0.5 · medium 0.2–0.49 · low < 0.2

Pocket 1 P2Rank #1

0.831

Likely same site as FPocket 4 0.4 Å 19 shared residues 100% of smaller site

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Surrounding area

Pocket 2 P2Rank #2

0.013

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Surrounding area

Pocket 3 P2Rank #3

0.012

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Surrounding area

Pocket 4 P2Rank #4

0.005

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Surrounding area

Binding pockets · FPocket

Druggability (FPocket): high ≥ 0.7 · medium 0.4–0.69 · low < 0.4

Pocket 1 FPocket #4

0.738

Likely same site as P2Rank 1 0.4 Å 19 shared residues 100% of smaller site

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Surrounding area

Pocket 2 FPocket #2

0.416

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Surrounding area

Residue sets

UniProt: Active site:126-126 Proton donor

UniProt: Binding site:12-12

UniProt: Binding site:124-124

UniProt: Binding site:167-167

UniProt: Binding site:197-197

UniProt: Binding site:225-225

UniProt: Binding site:226-226

UniProt: Binding site:227-227

UniProt: Binding site:269-269

UniProt: Binding site:41-41

UniProt: Binding site:74-74

UniProt: Binding site:96-96

All structural evidence 0 experimental · 2 predicted

Structural evidence

0 + 2

Experimental PDB entries plus predicted AlphaFold DB or ColabFold models. Click Switch to display a different loaded structure in the viewer.

Entry	Method	Resolution	Chain	Coverage	Links	Status
AlphaFold DB AF_A0A0H3GN13	AlphaFold DB	—	—	full sequence	—	Viewing
ColabFold VK055_2551	ColabFold	—	—	full sequence	—	Loaded

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.

32 records

Chemistry signal

Structural and bioactivity evidence are both available for this target.

Direct evidence 0 same-protein records

Transferred evidence 18 records from similar proteins

Structural ligands 17 0 loaded crystals

Measured bioactivity 1 direct and transferred ChEMBL records

Proposed compounds 14 similarity-based ZINC candidates

Best available ligand signal

0CG PDB via homolog 216.0 Da · LogP -0.15 · TPSA 113.3 Open detail RCSB PDB

0CH PDB via homolog Detail RCSB PDB

0CJ PDB via homolog Detail RCSB PDB

0CM PDB via homolog Detail RCSB PDB

0CN PDB via homolog Detail RCSB PDB

Highest-confidence structural evidence: ligands co-crystallized with this exact protein. If the source PDB is loaded in Target, 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 RCSB PDB	3URK	P62623	216.0 Da LogP -0.15 TPSA 113.3	✓ Ro5	✓ Clean	`C#CCOP(=O)(O)OP(=O)(O)O`
0CH RCSB PDB	3UV6	P62623	250.1 Da LogP -0.01 TPSA 133.5	✓ Ro5	✓ Clean	`C(CCOP(=O)(O)OP(=O)(O)O)CO`
0CJ RCSB PDB	3UTD	P62623	262.1 Da LogP 0.58 TPSA 130.4	✓ Ro5	✓ Clean	`CC(=O)CCCOP(=O)(O)OP(=O)(O)O`
0CM RCSB PDB	3UV3	P62623	230.0 Da LogP 0.24 TPSA 113.3	✓ Ro5	✓ Clean	`CC#CCOP(=O)(O)OP(=O)(O)O`
0CN RCSB PDB	3UV7	P62623	230.0 Da LogP 0.55 TPSA 113.3	✓ Ro5	✓ Clean	`C=C=CCOP(=O)(O)OP(=O)(O)O`
0JX RCSB PDB	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 RCSB PDB	3UWM	P62623	248.1 Da LogP 0.19 TPSA 130.4	✓ Ro5	✓ Clean	`C(CC=O)COP(=O)(O)OP(=O)(O)O`
0O3 RCSB PDB	4EB3	P62623	262.1 Da LogP 0.15 TPSA 133.5	✓ Ro5	✓ Clean	`C=C(CCOP(=O)(O)OP(=O)(O)O)CO`
10D RCSB PDB	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 RCSB PDB	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 RCSB PDB	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 RCSB PDB	3KEF	P62623	246.1 Da LogP 1.18 TPSA 113.3	✓ Ro5	✓ Clean	`CC(=CCO[P@@](=O)(O)OP(=O)(O)O)C`
EIP RCSB PDB	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 RCSB PDB	3F7T	P62623	295.8 Da LogP 2.59 TPSA 0.0	✓ Ro5	✓ Clean	`S1[Fe]2S[Fe]3[S]2[Fe]1S3`
H6P RCSB PDB	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 RCSB PDB	3KEM	P62623	246.1 Da LogP 1.18 TPSA 113.3	✓ Ro5	✓ Clean	`CC(=C)CCO[P@@](=O)(O)OP(=O)(O)O`
POP RCSB PDB	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 ChEMBL	O67625	7.22 ~60.3 nM	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 ZINC	1.000	246.1 Da LogP 1.18 TPSA 113.3	✓ Ro5	✓ Clean	`C=C(C)CCO[P@@](=O)(O)OP(=O)(O)O`
ZINC8215740 ZINC	1.000	246.1 Da LogP 1.18 TPSA 113.3	✓ Ro5	✓ Clean	`CC(C)=CCO[P@@](=O)(O)OP(=O)(O)O`
ZINC8436838 ZINC	1.000	262.1 Da LogP 0.15 TPSA 133.5	✓ Ro5	✓ Clean	`C/C(=C\CO[P@@](=O)(O)OP(=O)(O)O)CO`
ZINC71769106 ZINC	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 ZINC	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`
ZINC2579357 ZINC	0.700	248.1 Da LogP 1.26 TPSA 113.3	✓ Ro5	✓ Clean	`CC(C)CCO[P@](=O)(O)OP(=O)(O)O`
ZINC12494625 ZINC	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 ZINC	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 ZINC	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 ZINC	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 ZINC	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 ZINC	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 ZINC	0.520	212.1 Da LogP 1.04 TPSA 44.8	✓ Ro5	✓ Clean	`C#CCOP(=O)(OCC#C)OCC#C`
ZINC1532829 ZINC	0.500	234.2 Da LogP 2.79 TPSA 66.8	✓ Ro5	✓ Clean	`CC(C)=CCC/C(C)=C/COP(=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.

Cross-references

External database identifiers for this protein, its structures, ligands, and metabolic reactions.

4-hydroxy-3-methylbut-2-enyl diphosphate reductase

Strong target candidate with converging metabolic, structural and chemical evidence.

Main supporting evidence

Risks to review

Evidence coverage

Prioritization evidence

Off-target risk

Essentiality

Structure confidence

Binding-site evidence

Metabolic context

Sequence

Functional annotations

Subcellular localization

Enzyme Commission (EC)

Gene Ontology (GO)

Sequence domains and features

3D structure

Binding pockets · P2Rank

Binding pockets · FPocket

Binding pockets · P2Rank

Binding pockets · FPocket

Structural evidence

Ligand evidence

Cross-references

Sequence

Chemistry

Pathways