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Literature summary for 2.5.1.47 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

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

Cloned(Commentary)

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

Crystallization (Commentary)

Crystallization (Comment) Organism
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
the X-ray structure of three (MNWNI, MNYDI, and MNENI) high affinity pentapeptide-OASS complexes are compared with the docked poses Haemophilus influenzae

Inhibitors

Inhibitors Comment Organism Structure
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
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
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
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
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
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
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
MNLNI pentapeptide inhibitor; wild type pentapeptide of serine acetyltransferase Haemophilus influenzae
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
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
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
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
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
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)

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

Organism

Organism UniProt Comment Textmining
Haemophilus influenzae
-
-
-
Haemophilus influenzae P45040
-
-

Purification (Commentary)

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

Substrates and Products (Substrate)

Substrates Comment Substrates Organism Products Comment (Products) Rev. Reac.
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 ?
-
?
O3-acetyl-L-serine + hydrogen sulfide
-
Haemophilus influenzae L-cysteine + acetate
-
?

Synonyms

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

Cofactor

Cofactor Comment Organism Structure
pyridoxal 5'-phosphate
-
Haemophilus influenzae

Ki Value [mM]

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

General Information

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