Protein profile

PA5453

GDP-mannose 4,6-dehydratase

Genome: NC_002516.2

Gene: gmd gca PA5453 Structure source: Experimental + AlphaFold UniProt Q51366

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Amino acids 323

Annotations 8

Features 14

PDB binders 8

Druggability 0.292

Overview

Basic information about this protein and its source genome.

Accession: PA5453
Assembly: Pseudomonas aeruginosa PAO1, complete genome
Gene: gmd gca PA5453
Status: annotated
Amino acids: 323
Structure source: Experimental + AlphaFold

4.2.1.47

GO:0008446 Catalysis of the reaction: GDP-alpha-D-mannose = GDP-4-dehydro-6-deoxy-alpha-D-mannose + H2O. GO:0070401 Binding to the oxidized form, NADP+, of nicotinamide-adenine dinucleotide phosphate, a coenzyme involved in many redox and biosynthetic reactions. GO:0042351 The chemical reactions and pathways resulting in the formation of GDP-L-fucose from GDP-D-mannose via GDP-4-dehydro-6-deoxy-D-mannose, requiring the functions of GDP-mannose 4,6-dehydratase (EC:4.2.1.47) and GDP-L-fucose synthase (EC:1.1.1.271). GO:0019306 The chemical reactions and pathways resulting in the formation of GDP-D-rhamnose, a substance composed of rhamnose in glycosidic linkage with guanosine diphosphate. GO:0009103 The chemical reactions and pathways resulting in the formation of lipopolysaccharides, any of a group of related, structurally complex components of the outer membrane of Gram-negative bacteria. GO:0009243 The chemical reactions and pathways resulting in the formation of the O side chain of a lipopolysaccharide, which determines the antigenic specificity of the organism. It is made up of about 50 repeating units of a branched tetrasaccharide.

Target profile

Computed evidence for target prioritization.

Human off-target: hit
Human identity (%): 48.225
Human E-value: 5.0600000000000004e-110
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 0.292

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)

4.2.1.47

Gene Ontology (GO)

GO:0008446 Catalysis of the reaction: GDP-alpha-D-mannose = GDP-4-dehydro-6-deoxy-alpha-D-mannose + H2O.
GO:0070401 Binding to the oxidized form, NADP+, of nicotinamide-adenine dinucleotide phosphate, a coenzyme involved in many redox and biosynthetic reactions.
GO:0042351 The chemical reactions and pathways resulting in the formation of GDP-L-fucose from GDP-D-mannose via GDP-4-dehydro-6-deoxy-D-mannose, requiring the functions of GDP-mannose 4,6-dehydratase (EC:4.2.1.47) and GDP-L-fucose synthase (EC:1.1.1.271).
GO:0019306 The chemical reactions and pathways resulting in the formation of GDP-D-rhamnose, a substance composed of rhamnose in glycosidic linkage with guanosine diphosphate.
GO:0009103 The chemical reactions and pathways resulting in the formation of lipopolysaccharides, any of a group of related, structurally complex components of the outer membrane of Gram-negative bacteria.
GO:0009243 The chemical reactions and pathways resulting in the formation of the O side chain of a lipopolysaccharide, which determines the antigenic specificity of the organism. It is made up of about 50 repeating units of a branched tetrasaccharide.
GO:0019673 The chemical reactions and pathways involving GDP-mannose, a substance composed of mannose in glycosidic linkage with guanosine diphosphate.

Sequence Features

Domain/signature hits from InterPro and related databases.

14 records

Show feature table

Start	End	DB	Term	Name
186	312	Gene3D	G3DSA:3.90.25.10	-
6	302	Gene3D	G3DSA:3.40.50.720	-
1	208	FunFam	G3DSA:3.40.50.720:FF:000924	GDP-mannose 4,6 dehydratase
3	322	Hamap	MF_00955	GDP-mannose 4,6-dehydratase [gmd].
3	322	InterPro	IPR006368	GDP-mannose 4,6-dehydratase
4	319	NCBIfam	TIGR01472	GDP-mannose 4,6-dehydratase
4	319	InterPro	IPR006368	GDP-mannose 4,6-dehydratase
3	319	SUPERFAMILY	SSF51735	NAD(P)-binding Rossmann-fold domains
3	319	InterPro	IPR036291	NAD(P)-binding domain superfamily
5	318	CDD	cd05260	GDP_MD_SDR_e
6	312	Pfam	PF16363	GDP-mannose 4,6 dehydratase
6	312	InterPro	IPR016040	NAD(P)-binding domain
3	320	PANTHER	PTHR43715	GDP-MANNOSE 4,6-DEHYDRATASE
3	320	InterPro	IPR006368	GDP-mannose 4,6-dehydratase

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

1 + 1

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

Entry	Method	Resolution	Chain	Coverage	Links	Status
PDB 1RPN	X-ray	2.15 Å	A,B,C,D	100.0% 1-323	PDBe RCSB PDBj File	Viewing
AlphaFold PA5453	AlphaFold	—	—	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
1				0.292

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	61.45	0.988
2	2.54	0.071
3	1.03	0.006

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
5				0.292
2				0.207

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
6CK	5IN4	O60547	643.3 Da LogP -3.06 TPSA 311.5	3 viol.	✓ Clean	`c1nc2c(n1[C@H]3[C@@H]([C@@H]([C@H](O3)COP(=O)(O…`
A2R	2PK3	Q6T1X6	639.3 Da LogP -3.17 TPSA 338.0	3 viol.	✓ Clean	`c1nc(c2c(n1)n(cn2)[C@H]3[C@@H]([C@@H]([C@H](O3)…`
F7E	6GPL	O60547	587.3 Da LogP -3.39 TPSA 308.3	3 viol.	✓ Clean	`C[C@@H]1C(=O)[C@@H]([C@@H]([C@H](O1)OP(=O)(O)OP…`
G4F	6GPJ	O60547	607.3 Da LogP -3.65 TPSA 311.5	3 viol.	✓ Clean	`c1nc2c(n1[C@H]3[C@@H]([C@@H]([C@H](O3)COP(=O)(O…`
GDD	6GPK	O60547	605.3 Da LogP -4.63 TPSA 331.7	3 viol.	✓ Clean	`c1nc2c(n1[C@H]3[C@@H]([C@@H]([C@H](O3)CO[P@](=O…`
GDR	1N7G	P93031	589.3 Da LogP -3.60 TPSA 311.5	3 viol.	✓ Clean	`C[C@@H]1[C@H]([C@@H]([C@@H]([C@H](O1)O[P@@](=O)…`
GFB	5IN5	O60547	589.3 Da LogP -3.60 TPSA 311.5	3 viol.	✓ Clean	`C[C@H]1[C@H]([C@H]([C@@H]([C@H](O1)OP(=O)(O)OP(…`
POP	6X3B	Q9HTB6	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
CHEMBL4060134	O60547	—	482.5 Da LogP 1.75 TPSA 126.4	✓ Ro5	✓ Clean	`Cn1cnc(C(=O)N2CCN(C(=O)c3ccc(Nc4nc5ccccc5n5nnnc…`
CHEMBL4087470	O60547	—	452.5 Da LogP 2.17 TPSA 117.3	✓ Ro5	✓ Clean	`O=C(c1ccc(Nc2nc3ccccc3n3nnnc23)cc1)N1CCN(c2nccc…`

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
ZINC9561367	0.833	451.5 Da LogP 2.77 TPSA 104.4	✓ Ro5	✓ Clean	`O=C(c1ccc(Nc2nc3ccccc3n3nnnc23)cc1)N1CCN(c2cccc…`
ZINC205754446	0.769	482.5 Da LogP 1.75 TPSA 126.4	✓ Ro5	✓ Clean	`Cn1ccc(C(=O)N2CCN(C(=O)c3ccc(Nc4nc5ccccc5n5nnnc…`
ZINC104869865	0.750	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	0.750	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	0.750	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	0.750	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	0.750	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	0.750	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	0.750	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)(…`
ZINC6792710	0.733	375.4 Da LogP 1.89 TPSA 97.5	✓ Ro5	✓ Clean	`O=C(c1ccc(Nc2nc3ccccc3n3nnnc23)cc1)N1CCOCC1`
ZINC8594229	0.701	478.6 Da LogP 4.00 TPSA 91.5	✓ Ro5	✓ Clean	`Cc1ccc(C)c(N2CCN(C(=O)c3ccc(Nc4nc5ccccc5n5nnnc4…`
ZINC1532902	0.700	206.2 Da LogP -0.86 TPSA 132.1	✓ Ro5	✓ Clean	`O=C(O)CC[C@@](O)(CC(=O)O)C(=O)O`
ZINC2018106	0.700	206.2 Da LogP -0.86 TPSA 132.1	✓ Ro5	✓ Clean	`O=C(O)CC[C@](O)(CC(=O)O)C(=O)O`
ZINC12501413	0.691	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	0.691	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	0.691	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	0.691	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	0.691	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	0.691	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	0.691	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	0.691	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	0.691	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)[…`
ZINC3593496	0.652	206.2 Da LogP -1.16 TPSA 121.1	✓ Ro5	✓ Clean	`COC(=O)C[C@@](O)(CC(=O)O)C(=O)O`
ZINC3593497	0.652	206.2 Da LogP -1.16 TPSA 121.1	✓ Ro5	✓ Clean	`COC(=O)C[C@](O)(CC(=O)O)C(=O)O`
ZINC71774763	0.632	432.3 Da LogP -2.23 TPSA 198.3	1 viol.	✓ Clean	`Nc1nc2c(ncn2[C@@H]2O[C@H](CO[P@](=O)(O)N3CCOCC3…`
ZINC14686440	0.625	436.4 Da LogP -2.64 TPSA 247.9	1 viol.	✓ Clean	`O=C(O)C[C@](O)(CC(=O)NCCCCNC(=O)C[C@@](O)(CC(=O…`
ZINC14686442	0.625	436.4 Da LogP -2.64 TPSA 247.9	1 viol.	✓ Clean	`O=C(O)C[C@@](O)(CC(=O)NCCCCNC(=O)C[C@](O)(CC(=O…`
ZINC14686444	0.625	436.4 Da LogP -2.64 TPSA 247.9	1 viol.	✓ Clean	`O=C(O)C[C@@](O)(CC(=O)NCCCCNC(=O)C[C@@](O)(CC(=…`
ZINC9561297	0.614	468.5 Da LogP 3.52 TPSA 91.5	✓ Ro5	✓ Clean	`O=C(c1cccc(Nc2nc3ccccc3n3nnnc23)c1)N1CCN(c2ccc(…`
ZINC4743771	0.611	361.3 Da LogP -2.70 TPSA 182.6	1 viol.	✓ Clean	`CS(=O)(=O)OC[C@H]1O[C@@H](n2cnc3c(=O)[nH]c(N)nc…`
ZINC4743772	0.611	361.3 Da LogP -2.70 TPSA 182.6	1 viol.	✓ Clean	`CS(=O)(=O)OC[C@@H]1O[C@@H](n2cnc3c(=O)[nH]c(N)n…`
ZINC4743774	0.611	361.3 Da LogP -2.70 TPSA 182.6	1 viol.	✓ Clean	`CS(=O)(=O)OC[C@H]1O[C@@H](n2cnc3c(=O)[nH]c(N)nc…`
ZINC4743775	0.611	361.3 Da LogP -2.70 TPSA 182.6	1 viol.	✓ Clean	`CS(=O)(=O)OC[C@@H]1O[C@@H](n2cnc3c(=O)[nH]c(N)n…`
ZINC4412371	0.606	334.3 Da LogP 2.59 TPSA 94.3	✓ Ro5	✓ Clean	`CCOC(=O)c1ccc(Nc2nc3ccccc3n3nnnc23)cc1`
ZINC4412370	0.597	348.4 Da LogP 2.98 TPSA 94.3	✓ Ro5	✓ Clean	`CC(C)OC(=O)c1ccc(Nc2nc3ccccc3n3nnnc23)cc1`
ZINC12503703	0.579	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	0.579	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…`
ZINC13398039	0.577	234.2 Da LogP -0.38 TPSA 121.1	✓ Ro5	✓ Clean	`CC(C)OC(=O)C[C@](O)(CC(=O)O)C(=O)O`
ZINC2528012	0.577	234.2 Da LogP -0.38 TPSA 121.1	✓ Ro5	✓ Clean	`CC(C)OC(=O)C[C@@](O)(CC(=O)O)C(=O)O`
ZINC100058967	0.573	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	0.573	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	0.573	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	0.573	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(…`
ZINC1431865	0.571	262.3 Da LogP 2.42 TPSA 68.0	✓ Ro5	✓ Clean	`c1ccc(Nc2nc3ccccc3n3nnnc23)cc1`
ZINC6752117	0.571	306.3 Da LogP 2.11 TPSA 105.3	✓ Ro5	✓ Clean	`O=C(O)c1cccc(Nc2nc3ccccc3n3nnnc23)c1`
ZINC106686432	0.568	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…`
ZINC12958393	0.568	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	0.568	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)…`
ZINC80601236	0.568	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	0.568	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…`

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.