Candidate targets for in silico screening
The proteins in the table below have been identified as candidates for in silico screening by the NMPDR Drug Targets team. These represent a very limited set of proteins that have been determined to be essential in at least one of the NMPDR pathogens, have been included in subsystems by our curators, have orthologs in the Protein Data Bank, and have orthologs in a substantial number of the pathogenic bacterial species curated in the BRC system. These proteins will be used to optimize the virtual screening process. Results of the screening will be made available as it is generated.
These targets are also candidates for biochemical screening. To aid users interested in performing biochemical asays, the EC numbers of the targets are linked to functional infomation in the BRENDA database, and the PDB numbers are linked to those entries. To find these pegs in NMPDR, click on the name of the protein functional role.
| Protein Functional Role (EC info) (TC info) |
Subsystem | PDB | NMPDR page for PDB Source protein | Protein parameters | Orthologs in Priority pathogens | Candidacy based on |
|---|---|---|---|---|---|---|
| Cysteine desulfurase (EC 2.8.1.7) | Alanine Biosynthesis, Fe-S cluster assembly | 1p3w | Escherichia coli | homodimer | 34 |
essential in S. pneumo |
| Alanine racemase (EC 5.1.1.1) | Alanine Biosynthesis, Pyruvate Alanine Serine Interconversions | 1sft | Geobacillus stearothermophilus | homodimer or monomer | 21 |
essential in S. pneumo |
| Tryptophan synthase beta chain (EC 4.2.1.20) | Tryptophan synthesis | 1beu | Salmonella typhimurium | A2B2 tetramer | 23 |
essential in S. pneumo |
| S-adenosylmethionine synthetase (EC 2.5.1.6) | Methionine Biosynthesis, Polyamine Metabolism | 1rg9 | Escherichia coli | homotetramer | 30 |
essential in S. aureus, S. pneumo |
| Hydroxymethylglutaryl-CoA synthase (EC 2.3.3.10) | Isoprenoid Biosynthesis, Leucine Degradation and HMG-CoA Metabolism | 1xpk | Staphylococcus aureus subsp. aureus mw2 | homotetramer | 7 |
essential in S. pneumo |
| Glutamate racemase (EC 5.1.1.3) | Peptidoglycan Biosynthesis | 1b74 | Aquifex pyrophilus | homodimer or monomer | 27 |
essential in S. pneumo |
| UDP-N-acetylmuramate--alanine ligase (EC 6.3.2.8) | Peptidoglycan Biosynthesis | 1gqy | Haemophilus influenzae | homodimer | 31 |
essential in S. pneumo |
| UDP-N-acetylmuramoylalanine--D-glutamate ligase (EC 6.3.2.9) | Peptidoglycan Biosynthesis | 1eeh | Escherichia coli | monomer | 34 |
essential in S. pneumo |
| D-alanine--D-alanine ligase (EC 6.3.2.4) | Peptidoglycan Biosynthesis | 1ehi | Leuconostoc mesenteroides | homodimer | 33 |
essential in S. pneumo |
| UDP-N-acetylglucosamine 1-carboxyvinyltransferase (EC 2.5.1.7) | Peptidoglycan Biosynthesis, UDP-N-acetylmuramate from Fructose-6-phosphate Biosynthesis | 1naw | Enterobacter cloacae | homodimer or monomer | 34 |
essential in S. aureus |
| UDP-N-acetylenolpyruvoylglucosamine reductase (EC 1.1.1.158) | Peptidoglycan Biosynthesis, UDP-N-acetylmuramate from Fructose-6-phosphate Biosynthesis | 1hsk | Staphylococcus aureus | monomer | 32 |
essential in S. pneumo |
| Fructose-bisphosphate aldolase class II (EC 4.1.2.13) | Embden-Meyerhof and Gluconeogenesis | 1rvg | Thermus aquaticus | homotetramer | 27 |
essential in S. aureus, S. pneumo |
| Triosephosphate isomerase (EC 5.3.1.1) | Embden-Meyerhof and Gluconeogenesis | 2btm | Bacillus stearothermophilus | homodimer | 26 |
essential in S. pneumo |
| Pyruvate kinase (EC 2.7.1.40) | Embden-Meyerhof and Gluconeogenesis, Entner-Doudoroff Pathway, Fermentations: Mixed acid, Glyoxylate-Hydroxypyruvate Conversion, Pyruvate metabolism I: anaplerotic reactions PEP | 1e0u | Escherichia coli | homotetramer | 27 |
essential in S. aureus, S. pneumo |
| NAD-dependent glyceraldehyde-3-phosphate dehydrogenase (EC 1.2.1.12) | Embden-Meyerhof and Gluconeogenesis, Entner-Doudoroff Pathway, Pyridoxin (Vitamin B6) Biosynthesis | 1hdg | Thermotoga maritima | homodimer | 23 |
essential in S. aureus, S. pneumo |
| Glucose-6-phosphate isomerase (EC 5.3.1.9) | Embden-Meyerhof and Gluconeogenesis, Sucrose Metabolism | 1c7r | Bacillus stearothermophilus | monomer | 27 |
essential in S. aureus, S. pneumo |
| Gluconokinase (EC 2.7.1.12) | Entner-Doudoroff Pathway, Ketogluconate metabolism | 1xup | Enterococcus casseliflavus | homodimer | 16 |
essential in S. aureus |
| Ribulose-phosphate 3-epimerase (EC 5.1.3.1) | Pentose phosphate pathway | 2fli | Streptococcus pyogenes | homododecamer | 27 |
essential in S. pneumo |
| Transketolase (EC 2.2.1.1) | Pentose phosphate pathway, Ribose and deoxyribose phosphate metabolism | 1qgd | Escherichia coli | homodimer | 25 |
essential in S. aureus |
| 6-phosphofructokinase (EC 2.7.1.11) | D-Tagatose and Galactitol Utilization, Embden-Meyerhof and Gluconeogenesis, N-Acetyl-Galactosamine and Galactosamine Utilization | 6pfk | Bacillus stearothermophilus | homotetramer | 21 |
essential in S. aureus, S. pneumo |
| UDP-glucose 4-epimerase (EC 5.1.3.2) | Galactose degradation | 1sb9 | Pseudomonas aeruginosa | monomer | 26 |
essential in S. pneumo |
| Phosphate acetyltransferase (EC 2.3.1.8) | Ethanolamine utilization, Fermentations: Lactate, Fermentations: Mixed acid, Pyruvate metabolism II: acetyl-CoA acetogenesis from pyruvate | 1xco | Bacillus subtilis | homohexamer | 24 |
essential in S. aureus |
| Glycerol kinase (EC 2.7.1.30) | Glycerol and Glycerol-3-phosphate Uptake and Utilization, Glycerolipid and glycerphospholipid metabolism | 1r59 | Enterococcus casseliflavus | homodimer | 26 |
essential in S. aureus |
| Phosphopantothenoylcysteine decarboxylase (EC 4.1.1.36) | Coenzyme A Biosynthesis | 1u80 | Escherichia coli | homotrimer | 27 |
essential in S. pneumo |
| 2-amino-4-hydroxy-6-hydroxymethyldihydropteridine pyrophosphokinase (EC 2.7.6.3) | Folate Biosynthesis | 1cbk | Haemophilus influenzae | homodimer | 30 |
essential in S. pneumo |
| Dihydrofolate reductase (EC 1.5.1.3) | Folate Biosynthesis | 1ddr | Escherichia coli | homodimer | 30 |
essential in S. aureus, S. pneumo |
| Methionyl-tRNA formyltransferase (EC 2.1.2.9) | Folate Biosynthesis | 1fmt | Escherichia coli | homodimer | 34 |
essential in S. pneumo |
| Dihydroneopterin aldolase (EC 4.1.2.25) | Folate Biosynthesis | 2dhn | Staphylococcus aureus | homooctomer | 26 |
essential in S. pneumo |
| Dihydroneopterin aldolase / 2-amino-4-hydroxy-6-hydroxymethyldihydropteridine pyrophosphokinase (EC 4.1.2.25) / (EC 2.7.6.3) | Folate Biosynthesis | 2cg8 | Streptococcus pneumoniae | homotetramer | 2 |
essential in S. pneumo |
| Dihydropteroate synthase (EC 2.5.1.15) | Folate Biosynthesis | 1ad4 | Staphylococcus aureus | homodimer | 30 |
essential in S. pneumo |
| Serine hydroxymethyltransferase (EC 2.1.2.1) | Folate Biosynthesis, Glycine synthesis, Serine-glyoxylate cycle, Serine Biosynthesis | 1kl2 | Bacillus stearothermophilus | homodimer | 34 |
essential in S. aureus |
| Methylenetetrahydrofolate dehydrogenase (NADP+) / Methenyltetrahydrofolate cyclohydrolase (EC 1.5.1.5) / (EC 3.5.4.9) | Folate Biosynthesis, One-carbon metabolism by tetrahydropterines, Serine-glyoxylate cycle | 1B0A | Escherichia coli | monomer | 34 |
essential in S. pneumo |
| Thymidine kinase (EC 2.7.1.21) | Folate Biosynthesis, pyrimidine conversions | 1xx6 | Clostridium acetobutylicum | homodimer | 20 |
essential in S. aureus |
| Thymidylate synthase (EC 2.1.1.45) | Folate Biosynthesis, pyrimidine conversions | 4tms | Escherichia coli | homodimer | 25 |
essential in S. pneumo |
| Porphobilinogen deaminase (EC 2.5.1.61) | Porphyrin Heme and Siroheme Biosynthesis | 1pda | Escherichia coli | monomer | 29 |
essential in S. aureus |
| Holo-[acyl-carrier protein] synthase (EC 2.7.8.7) | Fatty Acid Biosynthesis FASII | 1fth | Streptococcus pneumoniae | homotrimer | 32 |
essential in S. pneumo |
| Phosphoribosylglycinamide formyltransferase (EC 2.1.2.2) | De Novo Purine Biosynthesis | 1jkx | Escherichia coli | monomer | 27 |
essential in S. pneumo |
| Amidophosphoribosyltransferase (EC 2.4.2.14) | De Novo Purine Biosynthesis | 1AO0 | Bacillus subtilis | homotetramer | 27 |
essential in S. aureus, S. pneumo |
| Adenylate kinase (EC 2.7.4.3) | Purine conversions | 1p3j | Bacillus subtilis | monomer | 34 |
essential in S. aureus, S. pneumo |
| Dihydroorotase (EC 3.5.2.3) | De Novo Pyrimidine Synthesis, Allantoin degradation | 1gkq | Pseudomonas aeruginosa | homodimer | 27 |
essential in S. aureus |
| Ribonucleotide reductase of class Ib (aerobic), alpha subunit (EC 1.17.4.1) | Ribonucleotide reduction | 1peu | Salmonella typhimurium | A2B2 tetramer | 17 |
essential in S. pneumo |
| Glutamyl-tRNA synthetase (EC 6.1.1.17) | Glu-tRNA(Gln) transamidation, Porphyrin Heme and Siroheme Biosynthesis, tRNA aminoacylation | 1n78 | Thermus thermophilus | monomer | 34 |
essential in S. aureus, S. pneumo |
| Enolase (EC 4.2.1.11) | Dehydrogenase complexes, Embden-Meyerhof and Gluconeogenesis, Entner-Doudoroff Pathway, Serine-glyoxylate cycle | 1w6t | Streptococcus pneumoniae | homodimer or homooctamer | 27 |
essential in S. aureus, S. pneumo |
| Dihydrolipoamide acetyltransferase component of pyruvate dehydrogenase complex (EC 2.3.1.12) | Dehydrogenase complexes, Glyoxylate dicarboxylate metabolism, Pyruvate metabolism II: acetyl-CoA acetogenesis from pyruvate | 1scz | Escherichia coli | 24-mer | 28 |
essential in S. aureus |
| Branched-chain alpha-keto acid dehydrogenase, E1 component, alpha subunit (EC 1.2.4.4) | Dehydrogenase complexes, Isoleucine degradation | 1qs0 | Pseudomonas putida | A2B2 tetramer | 12 |
essential in S. aureus |
| Branched-chain alpha-keto acid dehydrogenase, E1 component, beta subunit (EC 1.2.4.4) | Dehydrogenase complexes, Isoleucine degradation | 1um9 | Thermus thermophilus | A2B2 tetramer | 12 |
essential in S. aureus |