Protein profile

KP13_00977

2-succinyl-5-enolpyruvyl-6-hydroxy-3- cyclohexene-1-carboxylate synthase

Genome: KpKP13

Gene: menD AHE43493.1 Structure source: AlphaFold + ColabFold UniProt A0A0H3GVP4

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Amino acids 556

Annotations 7

Features 23

PDB binders 6

Druggability 0.729

Overview

Basic information about this protein and its source genome.

Accession: KP13_00977
Assembly: Klebsiella pneumoniae subsp. pneumoniae Kp13, complete sequence
Gene: menD AHE43493.1
Status: annotated
Amino acids: 556
Structure source: AlphaFold + ColabFold

2.2.1.9

GO:0009234 The chemical reactions and pathways resulting in the formation of any of the menaquinones. Structurally, menaquinones consist of a methylated naphthoquinone ring structure and side chains composed of a variable number of unsaturated isoprenoid residues. Menaquinones that have vitamin K activity and are known as vitamin K2. GO:0030976 Binding to thiamine pyrophosphate, the diphosphoric ester of thiamine. Acts as a coenzyme of several (de)carboxylases, transketolases, and alpha-oxoacid dehydrogenases. GO:0003824 Catalysis of a biochemical reaction at physiological temperatures. In biologically catalyzed reactions, the reactants are known as substrates, and the catalysts are naturally occurring macromolecular substances known as enzymes. Enzymes possess specific binding sites for substrates, and are usually composed wholly or largely of protein, but RNA that has catalytic activity (ribozyme) is often also regarded as enzymatic. GO:0070204 Catalysis of the reaction: 2-oxoglutarate + H+ + isochorismate = 5-enolpyruvoyl-6-hydroxy-2-succinyl-cyclohex-3-ene-1-carboxylate + CO2. GO:0000287 Binding to a magnesium (Mg) ion. GO:0030145 Binding to a manganese ion (Mn).

Target profile

Computed evidence for target prioritization.

Human off-target: No hit
Human identity (%): 0.0
Gut microbiome off-target: hit
Essential (DEG): Y
DEG identity (%): 48.233
DEG E-value: 2.0599999999999997e-180
Localization: Unknown
ColabFold pLDDT: 97.81

Selected Druggability evidence

AlphaFold / UniProt model

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 0.729

Structure A0A0H3GVP4

Pocket Pocket 14

P2Rank 0.619

Structure A0A0H3GVP4

Pocket Pocket 1

ColabFold model

FPocket 0.781 · Pocket 13

P2Rank 0.654 · Pocket 1

Core conservation Conserved core gene

Roary core

CoreCruncher core

Gut microbiome 104 / 4744 genomes with a hit

Normalized 0.022

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)

2.2.1.9

Gene Ontology (GO)

GO:0009234 The chemical reactions and pathways resulting in the formation of any of the menaquinones. Structurally, menaquinones consist of a methylated naphthoquinone ring structure and side chains composed of a variable number of unsaturated isoprenoid residues. Menaquinones that have vitamin K activity and are known as vitamin K2.
GO:0030976 Binding to thiamine pyrophosphate, the diphosphoric ester of thiamine. Acts as a coenzyme of several (de)carboxylases, transketolases, and alpha-oxoacid dehydrogenases.
GO:0003824 Catalysis of a biochemical reaction at physiological temperatures. In biologically catalyzed reactions, the reactants are known as substrates, and the catalysts are naturally occurring macromolecular substances known as enzymes. Enzymes possess specific binding sites for substrates, and are usually composed wholly or largely of protein, but RNA that has catalytic activity (ribozyme) is often also regarded as enzymatic.
GO:0070204 Catalysis of the reaction: 2-oxoglutarate + H+ + isochorismate = 5-enolpyruvoyl-6-hydroxy-2-succinyl-cyclohex-3-ene-1-carboxylate + CO2.
GO:0000287 Binding to a magnesium (Mg) ion.
GO:0030145 Binding to a manganese ion (Mn).

Sequence Features

Domain/signature hits from InterPro and related databases.

23 records

Show feature table

Start	End	DB	Term	Name
1	556	PIRSF	PIRSF004983	MenD
1	556	InterPro	IPR004433	2-succinyl-5-enolpyruvyl-6-hydroxy-3-cyclohexene-1-carboxylic-acid synthase
212	337	Gene3D	G3DSA:3.40.50.1220	-
4	553	Hamap	MF_01659	2-succinyl-5-enolpyruvyl-6-hydroxy-3-cyclohexene-1-carboxylate synthase [menD].
4	553	InterPro	IPR004433	2-succinyl-5-enolpyruvyl-6-hydroxy-3-cyclohexene-1-carboxylic-acid synthase
1	196	FunFam	G3DSA:3.40.50.970:FF:000029	2-succinyl-5-enolpyruvyl-6-hydroxy-3-cyclohexene-1-carboxylate synthase
348	556	Gene3D	G3DSA:3.40.50.970	-
184	388	Pfam	PF16582	Middle domain of thiamine pyrophosphate
184	388	InterPro	IPR032264	Menaquinone biosynthesis protein MenD, middle domain
362	552	SUPERFAMILY	SSF52518	Thiamin diphosphate-binding fold (THDP-binding)
362	552	InterPro	IPR029061	Thiamin diphosphate-binding fold
7	174	SUPERFAMILY	SSF52518	Thiamin diphosphate-binding fold (THDP-binding)
7	174	InterPro	IPR029061	Thiamin diphosphate-binding fold
414	534	Pfam	PF02775	Thiamine pyrophosphate enzyme, C-terminal TPP binding domain
414	534	InterPro	IPR011766	Thiamine pyrophosphate enzyme, TPP-binding
12	170	CDD	cd07037	TPP_PYR_MenD
10	430	NCBIfam	TIGR00173	2-succinyl-5-enolpyruvyl-6-hydroxy-3-cyclohexene-1-carboxylic-acid synthase
10	430	InterPro	IPR004433	2-succinyl-5-enolpyruvyl-6-hydroxy-3-cyclohexene-1-carboxylic-acid synthase
5	550	PANTHER	PTHR42916	2-SUCCINYL-5-ENOLPYRUVYL-6-HYDROXY-3-CYCLOHEXENE-1-CARBOXYLATE SYNTHASE
11	130	Pfam	PF02776	Thiamine pyrophosphate enzyme, N-terminal TPP binding domain
11	130	InterPro	IPR012001	Thiamine pyrophosphate enzyme, N-terminal TPP-binding domain
367	538	CDD	cd02009	TPP_SHCHC_synthase
1	196	Gene3D	G3DSA:3.40.50.970	-

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 + 2

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

Entry	Method	Resolution	Chain	Coverage	Links	Status
AlphaFold AF_A0A0H3GVP4	AlphaFold	—	—	full sequence	—	Viewing
ColabFold KP13_00977	ColabFold	—	—	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
14				0.729
3				0.637
15				0.421
34				0.34

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	7.47	0.392
2	4.1	0.165
3	1.58	0.024
4	1.33	0.015
5	0.85	0.003

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
13				0.781
2				0.414
6				0.374
39				0.205

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	Sticks	Spheres	Surfaces	Score	Probability	Labels	Zoom	Positions
1				8.4	0.448
2				3.94	0.156

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.

58 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
AKG	3HWW	P17109	146.1 Da LogP -0.50 TPSA 91.7	✓ Ro5	✓ Clean	`C(CC(=O)O)C(=O)C(=O)O`
DNA	6O0J	P9WK11	204.2 Da LogP 1.95 TPSA 77.8	✓ Ro5	✓ Clean	`c1ccc2c(c1)c(cc(c2O)C(=O)O)O`
ISC	5ESO	P9WK11	226.2 Da LogP -0.09 TPSA 104.1	✓ Ro5	✓ Clean	`C=C(C(=O)O)O[C@H]1C=CC=C([C@@H]1O)C(=O)O`
TD5	5EJM	P17109	527.4 Da LogP 0.74 TPSA 226.5	2 viol.	✓ Clean	`Cc1c(sc([n+]1Cc2cnc(nc2N)C)[C@@H](CCC(=O)O)O)CC…`
TD6	5EJ4	P17109	527.4 Da LogP 0.74 TPSA 226.5	2 viol.	✓ Clean	`Cc1c(sc([n+]1Cc2cnc(nc2N)C)[C@H](CCC(=O)O)O)CCO…`
TOI	5ESU	P9WK11	753.6 Da LogP -0.04 TPSA 331.3	3 viol.	✓ Clean	`[H]/N=C/1\C(=CNC(=N1)C)C[n+]2c(c(sc2[C@](CCC(=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
1CS	J7HAW4	8.15	357.8 Da LogP 1.35 TPSA 123.2	✓ Ro5	✓ Clean	`Cc1nc(nc(n1)OC)NC(=O)NS(=O)(=O)c2ccccc2Cl`
CHEMBL401913	J7HAW4	7.64	350.4 Da LogP 1.30 TPSA 138.3	✓ Ro5	✓ Clean	`Cc1cc(C)nc(NC(=O)NS(=O)(=O)c2ccccc2C(=O)O)n1`

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
ZINC1854808	1.000	350.4 Da LogP 1.30 TPSA 138.3	✓ Ro5	✓ Clean	`Cc1cc(C)nc(NC(=O)NS(=O)(=O)c2ccccc2C(=O)O)n1`
ZINC409255	1.000	204.2 Da LogP 1.95 TPSA 77.8	✓ Ro5	✓ Clean	`O=C(O)c1cc(O)c2ccccc2c1O`
ZINC186159	0.792	337.4 Da LogP 1.01 TPSA 123.2	✓ Ro5	✓ Clean	`COc1nc(C)nc(NC(=O)NS(=O)(=O)c2ccccc2C)n1`
ZINC1565922	0.769	430.4 Da LogP 3.87 TPSA 149.2	✓ Ro5	Alert	`O=C(O)c1cc(C(=O)C(=O)c2cc(C(=O)O)c(O)c3ccccc23)…`
ZINC22016278	0.765	461.1 Da LogP 2.87 TPSA 123.2	✓ Ro5	✓ Clean	`COc1nc(NC(=O)NS(=O)(=O)c2ccccc2Cl)nc(C(Cl)(Cl)C…`
ZINC2521491	0.765	373.8 Da LogP 1.06 TPSA 143.4	✓ Ro5	✓ Clean	`COc1nc(C)nc(NC(=O)NS(=O)(=O)c2cc(O)ccc2Cl)n1`
ZINC103209083	0.761	336.3 Da LogP 0.99 TPSA 138.3	✓ Ro5	✓ Clean	`Cc1ccnc(NC(=O)NS(=O)(=O)c2ccccc2C(=O)O)n1`
ZINC3176576	0.744	320.4 Da LogP 1.91 TPSA 101.0	✓ Ro5	✓ Clean	`Cc1cc(C)nc(NC(=O)NS(=O)(=O)c2ccccc2C)n1`
ZINC300799	0.711	340.8 Da LogP 2.26 TPSA 101.0	✓ Ro5	✓ Clean	`Cc1cc(C)nc(NC(=O)NS(=O)(=O)c2ccccc2Cl)n1`
ZINC18193628	0.692	370.8 Da LogP 1.41 TPSA 117.2	✓ Ro5	✓ Clean	`Cc1nc(NC(=O)NS(=O)(=O)c2ccccc2Cl)nc(N(C)C)n1`
ZINC1703286	0.690	202.2 Da LogP 2.45 TPSA 57.5	✓ Ro5	✓ Clean	`CC(=O)c1cc(O)c2ccccc2c1O`
ZINC394847	0.688	267.3 Da LogP 0.89 TPSA 117.7	✓ Ro5	✓ Clean	`NS(=O)(=O)c1cc(C(=O)O)c(O)c2ccccc12`
ZINC22204870	0.684	409.8 Da LogP 2.30 TPSA 136.3	✓ Ro5	✓ Clean	`COc1nc(NC(=O)NS(=O)(=O)c2ccccc2Cl)nc(-c2ccco2)n1`
ZINC104199149	0.667	444.4 Da LogP 4.26 TPSA 149.2	✓ Ro5	✓ Clean	`O=C(O)c1cc(C(=O)CC(=O)c2cc(C(=O)O)c(O)c3ccccc23…`
ZINC1565924	0.667	230.2 Da LogP 2.45 TPSA 74.6	✓ Ro5	✓ Clean	`CC(=O)c1cc(C(=O)O)c(O)c2ccccc12`
ZINC235999	0.667	267.1 Da LogP 3.01 TPSA 57.5	✓ Ro5	✓ Clean	`O=C(O)c1cc(Br)c2ccccc2c1O`
ZINC38337775	0.667	264.3 Da LogP 3.91 TPSA 57.5	✓ Ro5	✓ Clean	`O=C(O)c1cc(-c2ccccc2)c2ccccc2c1O`
ZINC4014517	0.667	222.6 Da LogP 2.90 TPSA 57.5	✓ Ro5	✓ Clean	`O=C(O)c1cc(Cl)c2ccccc2c1O`
ZINC59687703	0.667	206.2 Da LogP 2.38 TPSA 57.5	✓ Ro5	✓ Clean	`O=C(O)c1cc(F)c2ccccc2c1O`
ZINC3149462	0.660	371.8 Da LogP 1.38 TPSA 114.4	✓ Ro5	✓ Clean	`COc1nc(C)nc(N(C)C(=O)NS(=O)(=O)c2ccccc2Cl)n1`
ZINC902231	0.660	357.8 Da LogP 1.56 TPSA 126.7	✓ Ro5	✓ Clean	`COc1nc(C)nc(N/C(O)=N\S(=O)(=O)c2ccccc2Cl)n1`
ZINC1226893	0.655	440.7 Da LogP 2.53 TPSA 123.2	✓ Ro5	✓ Clean	`COc1nc(NC(=O)NS(=O)(=O)c2ccccc2C)nc(C(Cl)(Cl)Cl…`
ZINC2149641	0.636	280.3 Da LogP 3.47 TPSA 66.8	✓ Ro5	✓ Clean	`O=C(Oc1ccccc1)c1cc(O)c2ccccc2c1O`
ZINC3848736	0.633	340.8 Da LogP 2.26 TPSA 101.0	✓ Ro5	✓ Clean	`Cc1cc(Cl)nc(NC(=O)NS(=O)(=O)c2ccccc2C)n1`
ZINC3639593	0.627	365.4 Da LogP 0.79 TPSA 140.2	✓ Ro5	✓ Clean	`COC(=O)c1ccccc1S(=O)(=O)NC(=O)Nc1nc(C)nc(C)n1`
ZINC13335462	0.625	218.2 Da LogP 2.04 TPSA 66.8	✓ Ro5	✓ Clean	`COC(=O)c1cc(O)c2ccccc2c1O`
ZINC22016266	0.614	484.7 Da LogP 2.00 TPSA 149.5	✓ Ro5	✓ Clean	`COC(=O)c1ccccc1S(=O)(=O)NC(=O)Nc1nc(OC)nc(C(Cl)…`
ZINC22016269	0.614	395.4 Da LogP 0.88 TPSA 149.5	✓ Ro5	✓ Clean	`CCOc1nc(C)nc(NC(=O)NS(=O)(=O)c2ccccc2C(=O)OC)n1`
ZINC2275141	0.610	421.9 Da LogP 2.15 TPSA 131.8	✓ Ro5	✓ Clean	`Cc1cc(C)n(-c2nc(C)nc(NC(=O)NS(=O)(=O)c3ccccc3Cl…`
ZINC3848734	0.608	336.4 Da LogP 1.61 TPSA 110.3	✓ Ro5	✓ Clean	`COc1cc(C)nc(NC(=O)NS(=O)(=O)c2ccccc2C)n1`
ZINC22016313	0.607	351.4 Da LogP 1.26 TPSA 123.2	✓ Ro5	✓ Clean	`CCc1nc(NC(=O)NS(=O)(=O)c2ccccc2C)nc(OC)n1`
ZINC22016655	0.607	408.2 Da LogP 1.37 TPSA 148.1	✓ Ro5	✓ Clean	`COc1nc(C)nc(NC(=O)NS(=O)(=O)Nc2nc(Cl)ccc2Cl)n1`
ZINC35874338	0.603	493.2 Da LogP 1.00 TPSA 160.5	✓ Ro5	✓ Clean	`COc1nc(C)nc(NC(=O)NS(=O)(=O)c2cc(I)ccc2C(=O)O)n1`
ZINC1074291	0.593	433.9 Da LogP 3.10 TPSA 123.2	✓ Ro5	✓ Clean	`CCOc1nc(NC(=O)NS(=O)(=O)c2ccccc2Cl)nc(-c2ccccc2…`
ZINC221542346	0.593	450.5 Da LogP 1.52 TPSA 145.8	✓ Ro5	✓ Clean	`Cc1cc(C)nc(NC(=O)NS(=O)(=O)c2ccccc2C(=O)OC[C@@H…`
ZINC221542395	0.593	450.5 Da LogP 1.52 TPSA 145.8	✓ Ro5	✓ Clean	`Cc1cc(C)nc(NC(=O)NS(=O)(=O)c2ccccc2C(=O)OC[C@H]…`
ZINC221542457	0.593	450.5 Da LogP 1.52 TPSA 145.8	✓ Ro5	✓ Clean	`Cc1cc(C)nc(NC(=O)NS(=O)(=O)c2ccccc2C(=O)OC[C@@H…`
ZINC221542513	0.593	450.5 Da LogP 1.52 TPSA 145.8	✓ Ro5	✓ Clean	`Cc1cc(C)nc(NC(=O)NS(=O)(=O)c2ccccc2C(=O)OC[C@H]…`
ZINC754111	0.592	425.5 Da LogP 3.16 TPSA 104.3	✓ Ro5	✓ Clean	`Cc1cc(C)nc(NC(=O)NS(=O)(=O)N(Cc2ccccc2)Cc2ccccc…`
ZINC8215517	0.592	425.3 Da LogP 0.84 TPSA 169.0	✓ Ro5	✓ Clean	`Cc1ncc(C[n+]2csc(CCO[P@@](=O)(O)OP(=O)(O)O)c2C)…`
ZINC15218722	0.589	421.3 Da LogP 2.02 TPSA 136.1	✓ Ro5	✓ Clean	`COc1nc(C)nc(NC(=O)NS(=O)(=O)c2c(Cl)nc(C)c(Cl)c2…`
ZINC2243725	0.589	413.4 Da LogP 0.42 TPSA 150.9	✓ Ro5	✓ Clean	`COCCOc1ccccc1S(=O)(=O)NC(=O)Nc1nc(OC)nc(OC)n1`
ZINC2831367	0.583	423.5 Da LogP 1.66 TPSA 149.5	✓ Ro5	✓ Clean	`CCCCOc1nc(C)nc(NC(=O)NS(=O)(=O)c2ccccc2C(=O)OC)…`
ZINC1611750	0.581	204.2 Da LogP 1.95 TPSA 77.8	✓ Ro5	Alert	`O=C(O)c1cc2ccccc2c(O)c1O`
ZINC13335464	0.571	232.2 Da LogP 2.43 TPSA 66.8	✓ Ro5	✓ Clean	`CCOC(=O)c1cc(O)c2ccccc2c1O`
ZINC336013	0.571	246.2 Da LogP 2.17 TPSA 83.8	✓ Ro5	✓ Clean	`CC(=O)Oc1cc(C(=O)O)c(O)c2ccccc12`
ZINC13130640	0.569	395.4 Da LogP 0.74 TPSA 149.5	✓ Ro5	✓ Clean	`CCc1nc(NC(=O)NS(=O)(=O)c2ccccc2C(=O)OC)nc(OC)n1`
ZINC388870	0.566	328.2 Da LogP 3.14 TPSA 89.0	✓ Ro5	✓ Clean	`COc1nc(C)nc(NC(=O)Nc2ccc(Cl)c(Cl)c2)n1`
ZINC2831368	0.565	461.9 Da LogP 3.88 TPSA 123.2	✓ Ro5	✓ Clean	`CCCCOc1nc(NC(=O)NS(=O)(=O)c2ccccc2Cl)nc(-c2cccc…`
ZINC1182224	0.563	467.9 Da LogP 2.80 TPSA 138.8	✓ Ro5	✓ Clean	`CN(C)c1nc(NC(=O)NS(=O)(=O)c2ccccc2Cl)nc(ON=C2CC…`

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.