Protein profile

PA0400

cystathionine gamma-lyase

Genome: NC_002516.2

Gene: PA0400 Structure source: AlphaFold UniProt Q9I6A0

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Amino acids 394

Annotations 7

Features 18

PDB binders 6

Druggability 0.698

Overview

Basic information about this protein and its source genome.

Accession: PA0400
Assembly: Pseudomonas aeruginosa PAO1, complete genome
Gene: PA0400
Status: annotated
Amino acids: 394
Structure source: AlphaFold

GO:0005737 The contents of a cell excluding the plasma membrane and nucleus, but including other subcellular structures. GO:0004123 Catalysis of the reaction: L-cystathionine + H2O = 2-oxobutanoate + L-cysteine + NH4+. GO:0003962 Catalysis of the reaction: L-cysteine + O-succinyl-L-homoserine = H+ + L,L-cystathionine + succinate. GO:0030170 Binding to pyridoxal 5' phosphate, 3-hydroxy-5-(hydroxymethyl)-2-methyl4-pyridine carboxaldehyde 5' phosphate, the biologically active form of vitamin B6. GO:0019343 OBSOLETE. The chemical reactions and pathways resulting in the formation of L-cysteine, via the intermediate L-cystathionine. GO:0019346 The interconversion of homocysteine and cysteine via cystathionine. In contrast with enteric bacteria and mammals, Saccharomyces cerevisiae has two transsulfuration pathways employing two separate sets of enzymes.

Target profile

Computed evidence for target prioritization.

Human off-target: hit
Human identity (%): 52.231
Human E-value: 1.19e-128
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 0.698

Structure –

Pocket –

Sequence

Primary amino-acid sequence viewer.

Functional Annotations

Enzyme classification and Gene Ontology terms linked to this protein.

7 GO

Gene Ontology (GO)

GO:0005737 The contents of a cell excluding the plasma membrane and nucleus, but including other subcellular structures.
GO:0004123 Catalysis of the reaction: L-cystathionine + H2O = 2-oxobutanoate + L-cysteine + NH4+.
GO:0003962 Catalysis of the reaction: L-cysteine + O-succinyl-L-homoserine = H+ + L,L-cystathionine + succinate.
GO:0030170 Binding to pyridoxal 5' phosphate, 3-hydroxy-5-(hydroxymethyl)-2-methyl4-pyridine carboxaldehyde 5' phosphate, the biologically active form of vitamin B6.
GO:0019343 OBSOLETE. The chemical reactions and pathways resulting in the formation of L-cysteine, via the intermediate L-cystathionine.
GO:0019346 The interconversion of homocysteine and cysteine via cystathionine. In contrast with enteric bacteria and mammals, Saccharomyces cerevisiae has two transsulfuration pathways employing two separate sets of enzymes.
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.

Sequence Features

Domain/signature hits from InterPro and related databases.

18 records

Show feature table

Start	End	DB	Term	Name
13	258	FunFam	G3DSA:3.40.640.10:FF:000009	Cystathionine gamma-synthase homolog
17	391	Pfam	PF01053	Cys/Met metabolism PLP-dependent enzyme
17	391	InterPro	IPR000277	Cys/Met metabolism, pyridoxal phosphate-dependent enzyme
1	394	PIRSF	PIRSF001434	CGS
1	394	InterPro	IPR000277	Cys/Met metabolism, pyridoxal phosphate-dependent enzyme
260	393	FunFam	G3DSA:3.90.1150.10:FF:000008	Cystathionine gamma-synthase
17	393	SUPERFAMILY	SSF53383	PLP-dependent transferases
17	393	InterPro	IPR015424	Pyridoxal phosphate-dependent transferase
200	214	ProSitePatterns	PS00868	Cys/Met metabolism enzymes pyridoxal-phosphate attachment site.
200	214	InterPro	IPR000277	Cys/Met metabolism, pyridoxal phosphate-dependent enzyme
260	394	Gene3D	G3DSA:3.90.1150.10	Aspartate Aminotransferase, domain 1
260	394	InterPro	IPR015422	Pyridoxal phosphate-dependent transferase, small domain
15	393	PANTHER	PTHR11808	TRANS-SULFURATION ENZYME FAMILY MEMBER
15	393	InterPro	IPR000277	Cys/Met metabolism, pyridoxal phosphate-dependent enzyme
31	392	CDD	cd00614	CGS_like
31	392	InterPro	IPR000277	Cys/Met metabolism, pyridoxal phosphate-dependent enzyme
13	259	Gene3D	G3DSA:3.40.640.10	-
13	259	InterPro	IPR015421	Pyridoxal phosphate-dependent transferase, major domain

3D Structure

Selected loaded structure. Experimental PDB entries may cover only a portion of the sequence; predicted models typically cover the full protein.

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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 PA0400	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				0.698

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

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
0JO	4IYO	Q5H4T8	316.2 Da LogP 0.72 TPSA 149.5	✓ Ro5	✓ Clean	`Cc1c(c(c(cn1)COP(=O)(O)O)/C=N/C(=C)C(=O)O)O`
E9U	6LE4	F9UT53	451.4 Da LogP 0.11 TPSA 212.9	1 viol.	✓ Clean	`Cc1c(c(c(cn1)COP(=O)(O)O)/C=N/[C@@H](CCSC[C@@H]…`
F0G	6CJA	Q5ZX43	318.2 Da LogP 0.60 TPSA 149.5	✓ Ro5	✓ Clean	`Cc1c(c(c(cn1)COP(=O)(O)O)/C=N/[C@@H](C)C(=O)O)O`
KOU	6LDO	F9UT53	334.2 Da LogP -0.43 TPSA 169.8	✓ Ro5	✓ Clean	`Cc1c(c(c(cn1)COP(=O)(O)O)/C=N/C(CO)C(=O)O)O`
NAK	4IYO	Q5H4T8	87.1 Da LogP -3.04 TPSA 65.7	✓ Ro5	✓ Clean	`CC(=[NH2+])C(=O)[O-]`
PYR	6K1L	B4SII9	88.1 Da LogP -0.34 TPSA 54.4	✓ Ro5	✓ Clean	`CC(=O)C(=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
CHEMBL4795578	Q8VCN5	—	113.1 Da LogP -0.58 TPSA 63.3	✓ Ro5	✓ Clean	`C#CCC(N)C(=O)O`
QU4	Q8VCN5	—	422.3 Da LogP 2.45 TPSA 169.4	✓ Ro5	✓ Clean	`c1cc(c(cc1C(=C2C=CC(=O)C(=C2)C(=O)O)c3ccc(c(c3)…`

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
ZINC3833863	1.000	422.3 Da LogP 2.45 TPSA 169.4	✓ Ro5	✓ Clean	`O=C(O)C1=CC(=C(c2ccc(O)c(C(=O)O)c2)c2ccc(O)c(C(…`
ZINC2054344316	0.756	300.3 Da LogP 2.01 TPSA 111.9	✓ Ro5	✓ Clean	`CC(=C1C=CC(=O)C(C(=O)O)=C1)c1ccc(O)c(C(=O)O)c1`
ZINC28092924	0.756	300.3 Da LogP 2.01 TPSA 111.9	✓ Ro5	✓ Clean	`C/C(=C1/C=CC(=O)C(C(=O)O)=C1)c1ccc(O)c(C(=O)O)c1`
ZINC36748824	0.756	300.3 Da LogP 2.01 TPSA 111.9	✓ Ro5	✓ Clean	`C/C(=C1\C=CC(=O)C(C(=O)O)=C1)c1ccc(O)c(C(=O)O)c1`
ZINC1532514	0.646	247.1 Da LogP 0.52 TPSA 117.0	✓ Ro5	✓ Clean	`Cc1ncc(COP(=O)(O)O)c(C=O)c1O`
ZINC64708385	0.644	467.4 Da LogP 0.44 TPSA 214.5	1 viol.	✓ Clean	`NOC(=O)C1=CC(=C(c2ccc(O)c(C(=O)ON)c2)c2ccc(O)c(…`
ZINC2114966	0.643	332.2 Da LogP 0.99 TPSA 149.5	✓ Ro5	✓ Clean	`Cc1ncc(COP(=O)(O)O)c(/C=N/CCCC(=O)O)c1O`
ZINC6824902	0.576	401.2 Da LogP 3.22 TPSA 112.2	✓ Ro5	✓ Clean	`Cc1ncc(COP(=O)(O)O)c(/C=N/c2ccccc2Br)c1O`
ZINC2527979	0.564	296.3 Da LogP 0.32 TPSA 140.3	✓ Ro5	✓ Clean	`Cc1ncc(CO)c(/C=N/[C@@H](CCC(=O)O)C(=O)O)c1O`
ZINC1656021	0.551	233.2 Da LogP 1.01 TPSA 99.9	✓ Ro5	✓ Clean	`Cc1ncc(COP(=O)(O)O)c(C)c1O`
ZINC1532705	0.549	249.2 Da LogP 0.20 TPSA 120.1	✓ Ro5	✓ Clean	`Cc1ncc(COP(=O)(O)O)c(CO)c1O`
ZINC111474396	0.544	280.3 Da LogP 1.51 TPSA 103.0	✓ Ro5	✓ Clean	`CC[C@H](C)[C@H](/N=C\c1c(CO)cnc(C)c1O)C(=O)O`
ZINC2527980	0.544	280.3 Da LogP 1.51 TPSA 103.0	✓ Ro5	✓ Clean	`CC[C@H](C)[C@H](/N=C/c1c(CO)cnc(C)c1O)C(=O)O`
ZINC1532708	0.538	248.2 Da LogP 0.16 TPSA 125.9	✓ Ro5	✓ Clean	`Cc1ncc(COP(=O)(O)O)c(CN)c1O`
ZINC9944295	0.522	400.4 Da LogP 1.30 TPSA 149.4	✓ Ro5	✓ Clean	`Cc1ncc(COP(=O)(O)O)c(/C=N/NC(=S)NCc2ccco2)c1O`
ZINC12671061	0.520	346.4 Da LogP 4.29 TPSA 74.6	✓ Ro5	✓ Clean	`CC1=C/C(=C(/c2ccc(O)c(C)c2)c2ccccc2C(=O)O)C=CC1…`
ZINC3953836	0.520	346.4 Da LogP 4.29 TPSA 74.6	✓ Ro5	✓ Clean	`CC1=C/C(=C(\c2ccc(O)c(C)c2)c2ccccc2C(=O)O)C=CC1…`
ZINC12503280	0.510	302.2 Da LogP 1.01 TPSA 136.3	✓ Ro5	Alert	`O=C(O)C1=C/C(=N\Nc2ccc(O)c(C(=O)O)c2)C=CC1=O`
ZINC95536736	0.510	302.2 Da LogP 1.01 TPSA 136.3	✓ Ro5	Alert	`O=C(O)C1=C/C(=N/Nc2ccc(O)c(C(=O)O)c2)C=CC1=O`
ZINC127634755	0.500	228.2 Da LogP -1.62 TPSA 129.7	✓ Ro5	✓ Clean	`C#CC[C@H](NC(=O)[C@H](N)CC(=O)O)C(=O)O`
ZINC127634920	0.500	228.2 Da LogP -1.62 TPSA 129.7	✓ Ro5	✓ Clean	`C#CC[C@@H](NC(=O)[C@H](N)CC(=O)O)C(=O)O`
ZINC127635164	0.500	228.2 Da LogP -1.62 TPSA 129.7	✓ Ro5	✓ Clean	`C#CC[C@@H](NC(=O)[C@@H](N)CC(=O)O)C(=O)O`
ZINC1701223	0.500	302.2 Da LogP 1.73 TPSA 132.1	✓ Ro5	✓ Clean	`O=C(c1ccc(O)c(C(=O)O)c1)c1ccc(O)c(C(=O)O)c1`
ZINC2560970	0.500	228.2 Da LogP -1.62 TPSA 129.7	✓ Ro5	✓ Clean	`C#CC[C@H](NC(=O)[C@@H](N)CC(=O)O)C(=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.