KpATCC43816 Protein target profile

cysG

Accession: VK055_4401

Gene: cysG AIK82944.1 3D evidence: AlphaFold DB model + ColabFold model Metabolism 5 reactions UniProt A0A0H3GUG1
Length 457
Pocket druggability (P2Rank · AlphaFold DB model) 0.734
Metabolic reactions 5
Chokepoint Yes
Direct ligand evidence 0 4 total records
Functional annotation 0 EC 9 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.

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
2.7% of screened genomes Lower prevalence suggests narrower overlap with the screened gut microbiome.

Essentiality

Essential (DEG)
Y
DEG identity (%)
48.643 Higher values support similarity to known essential genes.
DEG E-value
1.78e-143 Smaller values mean stronger essential-gene similarity.

Structure confidence

ColabFold pLDDT
89.39 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) 0.734
Structure A0A0H3GUG1
Pocket Pocket 1
Druggability (FPocket) 0.752
Structure A0A0H3GUG1
Pocket Pocket 13
ColabFold model
P2Rank 0.828 · Pocket 1
FPocket 0.696 · Pocket 4
Core conservation Conserved core gene
Roary core
CoreCruncher core
Gut microbiome 128 / 4744 genomes with a hit
Prevalence 2.7%

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 Porphyrin metabolism, more central than 88.4% of genes in this genome, no human homolog detected.

Relative network centrality 88.4% more central than 88.4% of genes in this genome
Chokepoint Chokepoint gene
Catalyzed reactions

5 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.

MLVIGGGEIAERKIKFLLRAQAQVQVVAETLSPALADLAARQALSWRATAFSDSLVDDVFLVIAATEDEALNQRVFAAANARYRLVNVVDNQALCSFVFPSIVDRSPLLVAISSSGKAPVLSRILREKIEALLPTNLGRLAESASYWRNHLKTRLTTTEARRRFWERVFTGRFASLMVAGNSAEAEKALQDELDKPERETGEIILVGAGPGDAGLLTLRGLQAIQQADVVFHDHLVTQPVLELVRRDAELICVGKRAGEHSVPQHETNQLLVEAAKAGKTVVRLKGGDPFIFGRGAEELQAAAEAGIPFQVVPGVTAAAGATAYAGIPLTHRDYAQSAVFVTGHYKPDSAPFDWSLLAKSQQTLAIYMGTMKAAEISAQLIAHGRDSDTPVAVISRGTRDDQQTITGTLQQLEHLAKDAPMPALLVVGEVVQLHQQLAWFQHTSSAEGFNASVVNLA

Functional annotations

Enzyme classification and Gene Ontology terms linked to this protein.

9 GO

Subcellular localization

Localization
Cytoplasmic

Gene Ontology (GO)

9
  • GO:0051287 Binding to nicotinamide adenine dinucleotide, a coenzyme involved in many redox and biosynthetic reactions; binding may be to either the oxidized form, NAD+, or the reduced form, NADH.
  • GO:0019354 The chemical reactions and pathways resulting in the formation of siroheme, a tetrahydroporphyrin with adjacent, reduced pyrrole rings.
  • GO:0009236 The chemical reactions and pathways resulting in the formation of cobalamin (vitamin B12), a water-soluble vitamin characterized by possession of a corrin nucleus containing a cobalt atom.
  • GO:0043115 Catalysis of the reaction: NAD+ + precorrin-2 = 2 H+ + NADH + sirohydrochlorin.
  • GO:0008168 Catalysis of the transfer of a methyl group to an acceptor molecule.
  • GO:0051266 Catalysis of the reaction: siroheme + 2 H+ = Fe(2+) + sirohydrochlorin.
  • GO:0004851 Catalysis of the reaction: uroporphyrinogen III + 2 S-adenosyl-L-methionine = precorrin-2 + 2 S-adenosyl-L-homocysteine + H+.
  • GO:0006779 The chemical reactions and pathways resulting in the formation of any member of a large group of derivatives or analogs of porphyrin. Porphyrin consists of a ring of four pyrrole nuclei linked each to the next at their alpha positions through a methine group.
  • GO:0032259 The process in which a methyl group is covalently attached to a molecule.

Sequence domains and features

Domain and signature matches imported from InterPro and related databases.

38 records
Show feature table
Start End DB Term Name
197 316 FunFam G3DSA:3.40.1010.10:FF:000001 Siroheme synthase
99 134 FunFam G3DSA:3.30.160.110:FF:000001 Siroheme synthase
2 193 NCBIfam TIGR01470 siroheme synthase, N-terminal domain
2 193 InterPro IPR006367 Sirohaem synthase, N-terminal
2 99 SUPERFAMILY SSF51735 NAD(P)-binding Rossmann-fold domains
2 99 InterPro IPR036291 NAD(P)-binding domain superfamily
1 101 Pfam PF13241 Putative NAD(P)-binding
317 454 Gene3D G3DSA:3.30.950.10 -
317 454 InterPro IPR014776 Tetrapyrrole methylase, subdomain 2
1 98 Gene3D G3DSA:3.40.50.720 -
198 443 SUPERFAMILY SSF53790 Tetrapyrrole methylase
198 443 InterPro IPR035996 Tetrapyrrole methylase superfamily
281 314 ProSitePatterns PS00840 Uroporphyrin-III C-methyltransferase signature 2.
281 314 InterPro IPR003043 Uroporphiryn-III C-methyltransferase, conserved site
136 193 Pfam PF10414 Sirohaem synthase dimerisation region
136 193 InterPro IPR019478 Sirohaem synthase, dimerisation domain
206 220 ProSitePatterns PS00839 Uroporphyrin-III C-methyltransferase signature 1.
206 220 InterPro IPR003043 Uroporphiryn-III C-methyltransferase, conserved site
163 444 PANTHER PTHR45790 SIROHEME SYNTHASE-RELATED
135 193 Gene3D G3DSA:1.10.8.210 Sirohaem synthase, dimerisation domain
135 193 InterPro IPR037115 Sirohaem synthase, dimerisation domain superfamily
105 131 Pfam PF14824 Sirohaem biosynthesis protein central
105 131 InterPro IPR028281 Siroheme synthase, central domain
203 412 Pfam PF00590 Tetrapyrrole (Corrin/Porphyrin) Methylases
203 412 InterPro IPR000878 Tetrapyrrole methylase
201 434 NCBIfam TIGR01469 uroporphyrinogen-III C-methyltransferase
201 434 InterPro IPR006366 Uroporphyrin-III C-methyltransferase
194 316 Gene3D G3DSA:3.40.1010.10 -
194 316 InterPro IPR014777 Tetrapyrrole methylase, subdomain 1
99 134 Gene3D G3DSA:3.30.160.110 Siroheme synthase; domain 2
317 447 FunFam G3DSA:3.30.950.10:FF:000001 Siroheme synthase
100 194 SUPERFAMILY SSF75615 Siroheme synthase middle domains-like
1 443 Hamap MF_01646 Siroheme synthase [cysG].
1 443 InterPro IPR012409 Sirohaem synthase
206 431 CDD cd11642 SUMT
206 431 InterPro IPR006366 Uroporphyrin-III C-methyltransferase
1 450 PIRSF PIRSF036426 Sirohaem_synth
1 450 InterPro IPR012409 Sirohaem synthase

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
0.734
Likely same site as FPocket 13 4.4 Å 16 shared residues 76% of smaller site
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Surrounding area
Pocket 2 P2Rank #2
0.302
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Surrounding area
Pocket 3 P2Rank #3
0.242
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Surrounding area
Pocket 4 P2Rank #4
0.108
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Surrounding area
Pocket 5 P2Rank #5
0.037
Likely same site as FPocket 1 0.5 Å 11 shared residues 100% of smaller site
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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 #13
0.752 Unusual size
Likely same site as P2Rank 1 4.4 Å 16 shared residues 76% of smaller site
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Surrounding area
Pocket 2 FPocket #1
0.297
Likely same site as P2Rank 5 0.5 Å 11 shared residues 100% of smaller site
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Surrounding area
Residue sets
UniProt: Active site:244-244 Proton acceptor
UniProt: Active site:266-266 Proton donor
UniProt: Binding site:19-20
UniProt: Binding site:221-221
UniProt: Binding site:297-299
UniProt: Binding site:302-302
UniProt: Binding site:327-328
UniProt: Binding site:379-379
UniProt: Binding site:40-41
UniProt: Binding site:408-408
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_A0A0H3GUG1
AlphaFold DB full sequence Viewing
ColabFold VK055_4401
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.

4 records
Chemistry signal

Structural ligand evidence is available for this target.

Direct evidence 0 same-protein records
Transferred evidence 4 records from similar proteins
Structural ligands 4 0 loaded crystals
Measured bioactivity 0 direct and transferred ChEMBL records
Proposed compounds 0 similarity-based ZINC candidates
Best available ligand signal
FLC PDB via homolog 189.1 Da · LogP -5.25 · TPSA 140.6 Open detail RCSB PDB
PQ2 PDB via homolog Detail RCSB PDB
SHN PDB via homolog Detail RCSB PDB
UP2 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
FLC RCSB PDB Q5SKH6 189.1 Da LogP -5.25 TPSA 140.6 ✓ Ro5 ✓ Clean C(C(=O)[O-])C(CC(=O)[O-])(C(=O)[O-])O
PQ2 RCSB PDB P25924 864.9 Da LogP 3.78 TPSA 354.4 2 viol. ✓ Clean CC\1(C(/C/2=C/C3=N/C(=C\c4c(c(c([nH]4)Cc5c(c(c(…
SHN RCSB PDB P25924 862.8 Da LogP 4.69 TPSA 355.8 2 viol. ✓ Clean CC1(/c/2c/c3n/c(c\c4c(c(c([nH]4)cc5nc(/cc(\[nH]…
UP2 RCSB PDB P95417 836.8 Da LogP 2.25 TPSA 361.6 2 viol. ✓ Clean C1c2c(c(c([nH]2)Cc3c(c(c([nH]3)Cc4c(c(c([nH]4)C…

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.