Editing Active site (section)

===Competitive inhibitor: HIV protease inhibitor===
[[File:Indinavir, an HIV protease inhibitor.jpg|thumb|Indinavir, an HIV protease inhibitor.jpg|300px]]
[[Protease inhibitor (biology)|HIV protease inhibitors]] are used to treat patients having [[AIDS]] virus by preventing its [[DNA replication]]. [[HIV-1 protease|HIV protease]] is used by the virus to cleave Gag-Pol polyprotein into 3 smaller proteins that are responsible for virion assembly, package and maturation. This enzyme targets the specific [[phenylalanine]]-[[proline]] cleave site within the target protein.<ref name="Flexner">{{cite journal|vauthors=Flexner C|date=1998|title=HIV-protease inhibitors|journal=[[The New England Journal of Medicine]]|volume=338|issue=18|pages=1281–1292|doi=10.1056/NEJM199804303381808|pmid=9562584}}</ref> If HIV protease is switched off the virion particle will lose function and cannot infect patients. Since it is essential in viral replication and is absent in healthy human, it is an ideal target for [[drug development]].

HIV protease belongs to [[aspartic protease]] family and has a similar mechanism. Firstly the [[aspartate]] residue activates a water molecule and turns it into a [[nucleophile]]. Then it attacks the [[carbonyl group]] within the [[peptide bond]] (NH-CO) to form a tetrahedral intermediate. The nitrogen atom within the intermediate receives a proton, forming an [[amide|amide group]] and subsequent rearrangement leads to the breakdown of the bond between it and the intermediate and forms two products.<ref name="Ashraf">{{cite journal|vauthors=Ashraf B, Chi-Huey W|date=2003|title=HIV-1 protease: mechanism and drug discovery|journal=[[Organic & Biomolecular Chemistry]]|volume=1|issue=1|pages=5–14|doi=10.1039/B208248A|pmid=12929379}}</ref>

Inhibitors usually contain a nonhydrolyzable hydroxyethylene or hydroxyethylamine groups that mimic the tetrahedral intermediate. Since they share a similar structure and electrostatic arrangement to the [[transition state]] of substrates they can still fit into the active site but cannot be broken down, so hydrolysis cannot occur.