Sandbox Reserved 955: Difference between revisions
No edit summary |
No edit summary |
||
| Line 7: | Line 7: | ||
Proteases are one of the 3 (along with reverse transcriptases and integrases) virally encoded enzymes necessary for replication of immunodeffiency virus 1 <ref>http://en.wikipedia.org/wiki/HIV-1_protease</ref> (HIV-1). The protease is a member of the asparctic protease which cleaves the gag and pol polyproptein from the early life cycle of the virus. This cleavage is essential for the virus maturation to form functionnal small-sized proteins so that it can infect other cells. Without these proteases the virus cannot be infective. The enzyme is a dimer composed of two identical subunits forming a tunnel with the active site inside The mechanism of polypeptides cleavage uses a water molecule as a nucleophile simultaneously with a well-placed asparctic acid acid for hydrolysis of the scissile peptide bond. | Proteases are one of the 3 (along with reverse transcriptases and integrases) virally encoded enzymes necessary for replication of immunodeffiency virus 1 <ref>http://en.wikipedia.org/wiki/HIV-1_protease</ref> (HIV-1). The protease is a member of the asparctic protease which cleaves the gag and pol polyproptein from the early life cycle of the virus. This cleavage is essential for the virus maturation to form functionnal small-sized proteins so that it can infect other cells. Without these proteases the virus cannot be infective. The enzyme is a dimer composed of two identical subunits forming a tunnel with the active site inside The mechanism of polypeptides cleavage uses a water molecule as a nucleophile simultaneously with a well-placed asparctic acid acid for hydrolysis of the scissile peptide bond. | ||
The structure of HIV-1 protease with protein bound can't be solved as it would be cleaved before, we analyse how inhibitors bind to the active site to solve the structure | The structure of HIV-1 protease with protein bound can't be solved as it would be cleaved before, we analyse how inhibitors bind to the active site to solve the structure. | ||
Inhibitors like the hydroxyethylamine bind to the active site mimicking the tetrahedral transition state of the proteolytic reaction <ref>http://biology.kenyon.edu/BMB/Jmol2008/2uxz/index.html#Inhibitor</ref>. The inhibitor interacts with the active site by direct hydrogen bonds and indirect hydrogen bonds through water molecules. | Inhibitors like the hydroxyethylamine bind to the active site mimicking the tetrahedral transition state of the proteolytic reaction <ref>http://biology.kenyon.edu/BMB/Jmol2008/2uxz/index.html#Inhibitor</ref>. The inhibitor interacts with the active site by direct hydrogen bonds and indirect hydrogen bonds through water molecules. | ||
| Line 14: | Line 14: | ||
'''Inhibitor structure''' | '''Inhibitor structure''' | ||
The sequence of the inhibitor JG-365 is<scene name='60/604474/Inhibitor/1'>Ac-Ser-Leu-Asn-Phe-psi[CH(OH)CH2N]-Pro-Ile-Val-OMe</scene>; the Ki is 0.24 nM. It's a protein with a length of 7 amino acid residues, composed of a C chain.<ref>http://www.rcsb.org/pdb/explore/explore.do?structureId=7hvp</ref>.The orientation of the inhibitor is a particular one in the protease active site, in fact its flaps are folded directly over it in order to protect it from bulk solvent. | The sequence of the inhibitor JG-365 is <scene name='60/604474/Inhibitor/1'>Ac-Ser-Leu-Asn-Phe-psi[CH(OH)CH2N]-Pro-Ile-Val-OMe</scene>; the Ki is 0.24 nM. It's a protein with a length of 7 amino acid residues, composed of a C chain.<ref>http://www.rcsb.org/pdb/explore/explore.do?structureId=7hvp</ref>.The orientation of the inhibitor is a particular one in the protease active site, in fact its flaps are folded directly over it in order to protect it from bulk solvent. | ||
'''HIV 1 protease structure''' | '''HIV 1 protease structure''' | ||