Application | Comment | Organism |
---|---|---|
medicine | target for novel peptidomimetic antibiotics based on the C-terminal pentapeptide of serine acetyltransferase | Haemophilus influenzae |
Cloned (Comment) | Organism |
---|---|
expression in Escherichia coli BL21(DE3) with pET28a | Haemophilus influenzae |
HiOASS is overexpressed in Escherichia coli | Haemophilus influenzae |
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 | 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 | Organism | Comment (Nat. Sub.) | Natural Products | Comment (Nat. Pro.) | Rev. | Reac. |
---|---|---|---|---|---|---|
O3-acetyl-L-serine + hydrogen sulfide | Haemophilus influenzae | - |
L-cysteine + acetate | - |
? |
Organism | UniProt | Comment | Textmining |
---|---|---|---|
Haemophilus influenzae | - |
- |
- |
Haemophilus influenzae | P45040 | - |
- |
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 | 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 | Comment | Organism |
---|---|---|
HiOASS-A | - |
Haemophilus influenzae |
O-acetylserine sulfhydrylase | - |
Haemophilus influenzae |
OASS | - |
Haemophilus influenzae |
Cofactor | Comment | Organism | Structure |
---|---|---|---|
pyridoxal 5'-phosphate | - |
Haemophilus influenzae |
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 | Comment | Organism |
---|---|---|
malfunction | the inhibition of cysteine biosynthesis in prokaryotes and protozoa is proposed for the development of antibiotics | Haemophilus influenzae |