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Literature summary extracted from

  • Salsi, E.; Bayden, A.S.; Spyrakis, F.; Amadasi, A.; Campanini, B.; Bettati, S.; Dodatko, T.; Cozzini, P.; Kellogg, G.E.; Cook, P.F.; Roderick, S.L.; Mozzarelli, A.
    Design of O-acetylserine sulfhydrylase inhibitors by mimicking nature (2010), J. Med. Chem., 53, 345-356.
    View publication on PubMedView publication on EuropePMC

Application

EC Number Application Comment Organism
2.5.1.47 medicine target for novel peptidomimetic antibiotics based on the C-terminal pentapeptide of serine acetyltransferase Haemophilus influenzae

Cloned(Commentary)

EC Number Cloned (Comment) Organism
2.5.1.47 expression in Escherichia coli BL21(DE3) with pET28a Haemophilus influenzae
2.5.1.47 HiOASS is overexpressed in Escherichia coli Haemophilus influenzae

Crystallization (Commentary)

EC Number Crystallization (Comment) Organism
2.5.1.47 complex with inhibitory pentapeptides MNYDI (10 mM HEPES, pH 8.0, 25 mM NaCl, 8.8 mM peptide), MNKGI (20 mM HEPES, pH 7.5, 20 mM NaCl, 12.5 mM peptide), MNWNI (10 mM HEPES, pH 7.5, 25 mM NaCl, 7.5 mM peptide), MNYFI (20 mM HEPES, pH 8.0, 20 mM NaCl, 12.7 mM peptide), MNENI (10 mM HEPES, pH 7.5, 25 mM NaCl, 9.4 mM peptide), and MNETI (20 mM HEPES, pH 7.5, 20 mM NaCl, 9.4 mM peptide), reservoir solution is 100 mM HEPES, pH 7.5, between 1.8 and 2.1 M (NH4)2SO4, and polyethylene glycol 400, except for the complex with MNWNI (100 mM CAPS, pH 10.5, 1.75 (NH4)2SO4, and 0.2 M Li2SO4), the cryoprotection solution contains glycerol, hanging drop vapor diffusion method, diffraction data are measured at -183°C Haemophilus influenzae
2.5.1.47 the X-ray structure of three (MNWNI, MNYDI, and MNENI) high affinity pentapeptide-OASS complexes are compared with the docked poses Haemophilus influenzae

Inhibitors

EC Number Inhibitors Comment Organism Structure
2.5.1.47 MNDGI pentapeptide inhibitor; the C-terminal pentapeptide of serine acetyltransferase penetrates into the active site and competes with the substrate O3-acetyl-L-serine, thus inhibiting L-cysteine formation, essential contributor to the binding is the terminal Ile267 (80% interaction energy), Asn266 and Leu265 contribute 10% interaction energy each, pentapeptides of the structure MNxxI (xx are 2 exchangeable amino acids) have inhibitory action Haemophilus influenzae
2.5.1.47 MNEGI pentapeptide inhibitor; the C-terminal pentapeptide of serine acetyltransferase penetrates into the active site and competes with the substrate O3-acetyl-L-serine, thus inhibiting L-cysteine formation, essential contributor to the binding is the terminal Ile267 (80% interaction energy), Asn266 and Leu265 contribute 10% interaction energy each, pentapeptides of the structure MNxxI (xx are 2 exchangeable amino acids) have inhibitory action Haemophilus influenzae
2.5.1.47 MNENI pentapeptide inhibitor; the C-terminal pentapeptide of serine acetyltransferase penetrates into the active site and competes with the substrate O3-acetyl-L-serine, thus inhibiting L-cysteine formation, essential contributor to the binding is the terminal Ile267 (80% interaction energy), Asn266 and Leu265 contribute 10% interaction energy each, pentapeptides of the structure MNxxI (xx are 2 exchangeable amino acids) have inhibitory action Haemophilus influenzae
2.5.1.47 MNETI pentapeptide inhibitor; the C-terminal pentapeptide of serine acetyltransferase penetrates into the active site and competes with the substrate O3-acetyl-L-serine, thus inhibiting L-cysteine formation, essential contributor to the binding is the terminal Ile267 (80% interaction energy), Asn266 and Leu265 contribute 10% interaction energy each, pentapeptides of the structure MNxxI (xx are 2 exchangeable amino acids) have inhibitory action Haemophilus influenzae
2.5.1.47 MNKGI pentapeptide inhibitor; the C-terminal pentapeptide of serine acetyltransferase penetrates into the active site and competes with the substrate O3-acetyl-L-serine, thus inhibiting L-cysteine formation, essential contributor to the binding is the terminal Ile267 (80% interaction energy), Asn266 and Leu265 contribute 10% interaction energy each, pentapeptides of the structure MNxxI (xx are 2 exchangeable amino acids) have inhibitory action Haemophilus influenzae
2.5.1.47 MNKVI pentapeptide inhibitor; the C-terminal pentapeptide of serine acetyltransferase penetrates into the active site and competes with the substrate O3-acetyl-L-serine, thus inhibiting L-cysteine formation, essential contributor to the binding is the terminal Ile267 (80% interaction energy), Asn266 and Leu265 contribute 10% interaction energy each, pentapeptides of the structure MNxxI (xx are 2 exchangeable amino acids) have inhibitory action Haemophilus influenzae
2.5.1.47 MNLGI pentapeptide inhibitor; the C-terminal pentapeptide of serine acetyltransferase penetrates into the active site and competes with the substrate O3-acetyl-L-serine, thus inhibiting L-cysteine formation, essential contributor to the binding is the terminal Ile267 (80% interaction energy), Asn266 and Leu265 contribute 10% interaction energy each, pentapeptides of the structure MNxxI (xx are 2 exchangeable amino acids) have inhibitory action Haemophilus influenzae
2.5.1.47 MNLNI pentapeptide inhibitor; wild type pentapeptide of serine acetyltransferase Haemophilus influenzae
2.5.1.47 MNPHI pentapeptide inhibitor; the C-terminal pentapeptide of serine acetyltransferase penetrates into the active site and competes with the substrate O3-acetyl-L-serine, thus inhibiting L-cysteine formation, essential contributor to the binding is the terminal Ile267 (80% interaction energy), Asn266 and Leu265 contribute 10% interaction energy each, pentapeptides of the structure MNxxI (xx are 2 exchangeable amino acids) have inhibitory action Haemophilus influenzae
2.5.1.47 MNVPI pentapeptide inhibitor; the C-terminal pentapeptide of serine acetyltransferase penetrates into the active site and competes with the substrate O3-acetyl-L-serine, thus inhibiting L-cysteine formation, essential contributor to the binding is the terminal Ile267 (80% interaction energy), Asn266 and Leu265 contribute 10% interaction energy each, pentapeptides of the structure MNxxI (xx are 2 exchangeable amino acids) have inhibitory action Haemophilus influenzae
2.5.1.47 MNWNI pentapeptide inhibitor; the C-terminal pentapeptide of serine acetyltransferase penetrates into the active site and competes with the substrate O3-acetyl-L-serine, thus inhibiting L-cysteine formation, essential contributor to the binding is the terminal Ile267 (80% interaction energy), Asn266 and Leu265 contribute 10% interaction energy each, pentapeptides of the structure MNxxI (xx are 2 exchangeable amino acids) have inhibitory action Haemophilus influenzae
2.5.1.47 MNYDI pentapeptide inhibitor; the C-terminal pentapeptide of serine acetyltransferase penetrates into the active site and competes with the substrate O3-acetyl-L-serine, thus inhibiting L-cysteine formation, essential contributor to the binding is the terminal Ile267 (80% interaction energy), Asn266 and Leu265 contribute 10% interaction energy each, pentapeptides of the structure MNxxI (xx are 2 exchangeable amino acids) have inhibitory action Haemophilus influenzae
2.5.1.47 MNYFI pentapeptide inhibitor; the C-terminal pentapeptide of serine acetyltransferase penetrates into the active site and competes with the substrate O3-acetyl-L-serine, thus inhibiting L-cysteine formation, essential contributor to the binding is the terminal Ile267 (80% interaction energy), Asn266 and Leu265 contribute 10% interaction energy each, pentapeptides of the structure MNxxI (xx are 2 exchangeable amino acids) have inhibitory action Haemophilus influenzae
2.5.1.47 MNYSI pentapeptide inhibitor; the C-terminal pentapeptide of serine acetyltransferase penetrates into the active site and competes with the substrate O3-acetyl-L-serine, thus inhibiting L-cysteine formation, essential contributor to the binding is the terminal Ile267 (80% interaction energy), Asn266 and Leu265 contribute 10% interaction energy each, pentapeptides of the structure MNxxI (xx are 2 exchangeable amino acids) have inhibitory action Haemophilus influenzae

Natural Substrates/ Products (Substrates)

EC Number Natural Substrates Organism Comment (Nat. Sub.) Natural Products Comment (Nat. Pro.) Rev. Reac.
2.5.1.47 O3-acetyl-L-serine + hydrogen sulfide Haemophilus influenzae
-
 L-cysteine + acetate
-
 ?

Organism

EC Number Organism UniProt Comment Textmining
2.5.1.47 Haemophilus influenzae
-
-
-
2.5.1.47 Haemophilus influenzae P45040
-
-

Purification (Commentary)

EC Number Purification (Comment) Organism
2.5.1.47 Ni-NTA affinity and Superdex 200 pg gel filtration chromatography Haemophilus influenzae
2.5.1.47 using Ni-NTA chromatography and gel filtration Haemophilus influenzae

Substrates and Products (Substrate)

EC Number Substrates Comment Substrates Organism Products Comment (Products) Rev. Reac.
2.5.1.47 additional information the binding free energy of 400 pentapeptides, MNXXI, interacting with the HiOASS-A active site using a combined docking-scoring procedure based on GOLD and HINTare examined. The free energy prediction is verified by the experimental determination of the binding affinity of 14 of these pentapeptides, selected for spanning a large range of predicted binding affinity and presenting charged, polar, or apolar residues at mutation sites Haemophilus influenzae ?
-
 ?
2.5.1.47 O3-acetyl-L-serine + hydrogen sulfide
-
 Haemophilus influenzae L-cysteine + acetate
-
 ?

Synonyms

EC Number Synonyms Comment Organism
2.5.1.47 HiOASS-A
-
 Haemophilus influenzae
2.5.1.47 O-acetylserine sulfhydrylase
-
 Haemophilus influenzae
2.5.1.47 OASS
-
 Haemophilus influenzae

Cofactor

EC Number Cofactor Comment Organism Structure
2.5.1.47 pyridoxal 5'-phosphate
-
 Haemophilus influenzae

Ki Value [mM]

EC Number Ki Value [mM] Ki Value maximum [mM] Inhibitor Comment Organism Structure
2.5.1.47 0.0249
-
 MNWNI 100 mM HEPES, pH 7.0, 1 microM enzyme, 20°C, steady state fluorescence titration Haemophilus influenzae
2.5.1.47 0.0258
-
 MNYDI 100 mM HEPES, pH 7.0, 1 microM enzyme, 20°C, steady state fluorescence titration Haemophilus influenzae
2.5.1.47 0.0387
-
 MNENI 100 mM HEPES, pH 7.0, 1 microM enzyme, 20°C, steady state fluorescence titration Haemophilus influenzae
2.5.1.47 0.044
-
 MNLNI wild type serine acetyltransferase motif, 100 mM HEPES, pH 7.0, 1 microM enzyme, 20°C, steady state fluorescence titration Haemophilus influenzae
2.5.1.47 0.0608
-
 MNYSI 100 mM HEPES, pH 7.0, 1 microM enzyme, 20°C, steady state fluorescence titration Haemophilus influenzae
2.5.1.47 0.191
-
 MNYFI 100 mM HEPES, pH 8.0, 1 microM enzyme, 20°C, steady state fluorescence titration Haemophilus influenzae
2.5.1.47 0.57
-
 MNLGI 100 mM HEPES, pH 7.0, 1 microM enzyme, 20°C, steady state fluorescence titration Haemophilus influenzae
2.5.1.47 1.03
-
 MNDGI 100 mM HEPES, pH 7.0, 1 microM enzyme, 20°C, steady state fluorescence titration Haemophilus influenzae
2.5.1.47 2.27
-
 MNEGI 100 mM HEPES, pH 7.0, 1 microM enzyme, 20°C, steady state fluorescence titration Haemophilus influenzae
2.5.1.47 3.33
-
 MNVPI 100 mM HEPES, pH 7.0, 1 microM enzyme, 20°C, steady state fluorescence titration Haemophilus influenzae
2.5.1.47 3.42
-
 MNETI 100 mM HEPES, pH 7.0, 1 microM enzyme, 20°C, steady state fluorescence titration Haemophilus influenzae
2.5.1.47 7.1
-
 MNPHI 100 mM HEPES, pH 7.0, 1 microM enzyme, 20°C, steady state fluorescence titration Haemophilus influenzae
2.5.1.47 13.3
-
 MNKVI 100 mM HEPES, pH 7.0, 1 microM enzyme, 20°C, steady state fluorescence titration Haemophilus influenzae
2.5.1.47 15.2
-
 MNKGI 100 mM HEPES, pH 7.0, 1 microM enzyme, 20°C, steady state fluorescence titration Haemophilus influenzae

General Information

EC Number General Information Comment Organism
2.5.1.47 malfunction the inhibition of cysteine biosynthesis in prokaryotes and protozoa is proposed for the development of antibiotics Haemophilus influenzae