KpATCC43816 Protein target profile

argininosuccinate synthase

Accession: VK055_3898

Gene: AIK82447.1 argG 3D evidence: AlphaFold DB model + ColabFold model Metabolism 2 reactions UniProt A0A0H3GY11
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Length 447
Pocket druggability (P2Rank · AlphaFold DB model) 0.855
Metabolic reactions 2
Chokepoint Yes
Direct ligand evidence 0 56 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

Metabolic chokepoint Catalyzes a reaction that is the only producer or consumer of a metabolite in the imported metabolic model. Central metabolic position More central than 98.6% of genes in this genome. No isoenzyme backup detected Imported GPR rules do not show an alternative enzyme for the catalyzed reaction set. Core gene across strains Marked as conserved by both pan-genome tools: Roary and CoreCruncher. Review the complete evidence below

Risks to review

Low human similarity A human hit was flagged, but identity is only 29.592% - a weak match, lower risk than a close homolog. This target also has a predicted binding pocket (P2Rank 0.85) — check the ligand evidence before deprioritizing on off-target risk alone. Microbiome similarity 186 of 4744 screened genomes (3.9%) have a significant similarity hit. This target also has a predicted binding pocket (P2Rank 0.85) — check the ligand evidence before deprioritizing on off-target risk alone. Best pocket may be a modeling artifact FPocket selected-pocket score 0.55, but this pocket's geometry is unusually large/diffuse compared to this protein's other predicted pockets — may reflect a low-confidence or disordered model region rather than a real cavity.

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
Hit
Human identity (%)
29.592 Lower values reduce human off-target concern.
Human E-value
3.31e-18
Gut microbiome similarity
3.9% of screened genomes Lower prevalence suggests narrower overlap with the screened gut microbiome.

Essentiality

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

Structure confidence

ColabFold pLDDT
96.04 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) 0.855
Structure A0A0H3GY11
Pocket Pocket 1
Druggability (FPocket) 0.554
Structure A0A0H3GY11
Pocket Pocket 1
ColabFold model
P2Rank 0.862 · Pocket 1
FPocket 0.692 · Pocket 18
Core conservation Conserved core gene
Roary core
CoreCruncher core
Gut microbiome 186 / 4744 genomes with a hit
Prevalence 3.9%

Metabolic context

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

Explore metabolic network

Attractive metabolic target: catalyzes a producing chokepoint reaction in Alanine, aspartate and glutamate metabolism, no isoenzyme backup detected, more central than 98.6% of genes in this genome.

Relative network centrality 98.6% more central than 98.6% of genes in this genome
Chokepoint Chokepoint gene
Pathways
Alanine, aspartate and glutamate metabolism Arginine biosynthesis
Catalyzed reactions

2 reactions mapped to this gene in the metabolic model. Open the full network to see each one, with substrates/products and the reaction-reaction map.

Imported from KpATCC43816.sbml · 2026-07-09

Sequence

Primary amino-acid sequence viewer.

MTTILKHLPVGQRIGIAFSGGLDTSAALLWMRKKGAVPYAYTANLGQPDEDDYDAIPRRAKEYGAEGARLIDCRKQLVAEGIAAIQCGAFHNTTGGLTYFNTTPLGRAVTGTMLVAAMKEDGVNIWGDGSTYKGNDIERFYRYGLLTNAELQIYKPWLDSDFINELGGRHEMSEFMIACGFDYKMSVEKAYSTDSNMLGATHEAKDLEFLNSSVKIVNPIMGVKFWDENVKIPAEEVTVRFEQGHPVALNGKTFADDVEMMLEANRIGGRHGLGMSDQIENRIIEAKSRGIYEAPGMALLHIAYERLLTGIHNEDTIEQYHAHGRQLGRLLYQGRWFDSQALMLRDSLQRWVASQITGEVTLELRRGNDYSILNTVSDNLTYKAERLTMEKGDSMFTAEDRIGQLTMRNLDITDTREKLFGYAQSGLLSASSATGLPQVENLENKGK

Functional annotations

Enzyme classification and Gene Ontology terms linked to this protein.

1 EC 7 GO

Subcellular localization

Localization
Cytoplasmic

Enzyme Commission (EC)

1

Gene Ontology (GO)

7
  • GO:0004055 Catalysis of the reaction: ATP + L-citrulline + L-aspartate = AMP + diphosphate + (N(omega)-L-arginino)succinate.
  • GO:0005524 Binding to ATP, adenosine 5'-triphosphate, a universally important coenzyme and enzyme regulator.
  • GO:0006526 The chemical reactions and pathways resulting in the formation of arginine, 2-amino-5-(carbamimidamido)pentanoic acid.
  • GO:0042803 Binding to an identical protein to form a homodimer.
  • GO:0005737 The contents of a cell excluding the plasma membrane and nucleus, but including other subcellular structures.
  • GO:0000053 OBSOLETE. The chemical reactions and pathways involving argininosuccinate, 2-(N(omega)-arginino)succinate, an intermediate in the ornithine-urea cycle, where it is synthesized from citrulline and aspartate.
  • GO:0000050 The sequence of reactions by which arginine is synthesized from ornithine, then cleaved to yield urea and regenerate ornithine. The overall reaction equation is NH3 + CO2 + aspartate + 3 ATP + 2 H2O = urea + fumarate + 2 ADP + 2 phosphate + AMP + diphosphate.

Sequence domains and features

Domain and signature matches imported from InterPro and related databases.

22 records
Show feature table
Start End DB Term Name
16 408 Pfam PF00764 Arginosuccinate synthase
16 408 InterPro IPR001518 Argininosuccinate synthase
377 442 FunFam G3DSA:1.10.287.400:FF:000001 Argininosuccinate synthase
1 443 Hamap MF_00581 Argininosuccinate synthase [argG].
1 443 InterPro IPR023437 Argininosuccinate synthase, type 2 subfamily
12 417 PANTHER PTHR11587 ARGININOSUCCINATE SYNTHASE
12 417 InterPro IPR001518 Argininosuccinate synthase
13 419 NCBIfam TIGR00032 argininosuccinate synthase
13 419 InterPro IPR001518 Argininosuccinate synthase
3 186 SUPERFAMILY SSF52402 Adenine nucleotide alpha hydrolases-like
377 440 Gene3D G3DSA:1.10.287.400 -
377 440 InterPro IPR024073 Argininosuccinate synthetase mutimerisation domain, C-terminal tail
13 190 Gene3D G3DSA:3.40.50.620 HUPs
13 190 InterPro IPR014729 Rossmann-like alpha/beta/alpha sandwich fold
17 25 ProSitePatterns PS00564 Argininosuccinate synthase signature 1.
17 25 InterPro IPR018223 Argininosuccinate synthase, conserved site
74 370 Gene3D G3DSA:3.90.1260.10 Argininosuccinate synthetase, chain A, domain 2
74 370 InterPro IPR024074 Argininosuccinate synthetase, catalytic/multimerisation domain body
190 444 SUPERFAMILY SSF69864 Argininosuccinate synthetase, C-terminal domain
190 444 InterPro IPR024074 Argininosuccinate synthetase, catalytic/multimerisation domain body
129 140 ProSitePatterns PS00565 Argininosuccinate synthase signature 2.
129 140 InterPro IPR018223 Argininosuccinate synthase, conserved site

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
0.855
Likely same site as FPocket 1 6.4 Å 23 shared residues 64% of smaller site
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Surrounding area
Pocket 2 P2Rank #2
0.626
Likely same site as FPocket 1 7.6 Å 15 shared residues 83% of smaller site
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Surrounding area
Pocket 3 P2Rank #3
0.326
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Surrounding area
Pocket 4 P2Rank #4
0.118
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Surrounding area
Pocket 5 P2Rank #5
0.006
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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 #1
0.554 Unusual size
Likely same site as P2Rank 1 6.4 Å 23 shared residues 64% of smaller site
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Surrounding area
Residue sets
UniProt: Binding site:129-129
UniProt: Binding site:131-131
UniProt: Binding site:135-135
UniProt: Binding site:136-136
UniProt: Binding site:139-139
UniProt: Binding site:17-25
UniProt: Binding site:192-192
UniProt: Binding site:194-194
UniProt: Binding site:201-201
UniProt: Binding site:203-203
UniProt: Binding site:280-280
UniProt: Binding site:43-43
UniProt: Binding site:99-99
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_A0A0H3GY11
AlphaFold DB — — full sequence — Viewing
ColabFold VK055_3898
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.

56 records
Chemistry signal

Structural ligand evidence is available for this target.

Direct evidence 0 same-protein records
Transferred evidence 6 records from similar proteins
Structural ligands 6 0 loaded crystals
Measured bioactivity 0 direct and transferred ChEMBL records
Proposed compounds 50 similarity-based ZINC candidates
Best available ligand signal
ADN PDB via homolog 267.2 Da · LogP -1.98 · TPSA 139.5 Open detail RCSB PDB
ANP PDB via homolog Detail RCSB PDB
AS1 PDB via homolog Detail RCSB PDB
CIR PDB via homolog Detail RCSB PDB
MLA PDB via homolog Detail RCSB PDB

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.

Show only:
Ligand Source crystal UniProt (homolog) MW · LogP · TPSA Lipinski PAINS SMILES
ADN RCSB PDB
5US8
Q7VTJ9 267.2 Da LogP -1.98 TPSA 139.5 ✓ Ro5 ✓ Clean c1nc(c2c(n1)n(cn2)[C@H]3[C@@H]([C@@H]([C@H](O3)…
ANP RCSB PDB
4XFJ
G7CBN9 506.2 Da LogP -2.06 TPSA 281.9 3 viol. ✓ Clean c1nc(c2c(n1)n(cn2)[C@H]3[C@@H]([C@@H]([C@H](O3)…
AS1 RCSB PDB
1J20
P59846 290.3 Da LogP -1.99 TPSA 188.3 1 viol. ✓ Clean C(C[C@@H](C(=O)O)N)C/N=C(\N)/N[C@@H](CC(=O)O)C(…
CIR RCSB PDB
1K97
P0A6E4 175.2 Da LogP -1.15 TPSA 118.4 ✓ Ro5 ✓ Clean C(C[C@@H](C(=O)O)N)CNC(=O)N
MLA RCSB PDB
6E5Y
Q7VTJ9 104.1 Da LogP -0.45 TPSA 74.6 ✓ Ro5 ✓ Clean C(C(=O)O)C(=O)O
SIN RCSB PDB
1KOR
P59846 118.1 Da LogP -0.06 TPSA 74.6 ✓ Ro5 ✓ Clean C(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.

Cross-references

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

Sequence

UniProt A0A0H3GY11

Pathways

BioCyc RXN-10 KEGG R01954 BioCyc ARGSUCCINSYN-RXN