Papain: Difference between revisions

The goal of research for the development of an inhibitor for <scene name='Papain/Cathepsin_k/2'>Cathepsin K</scene> is the hope to develop a treatment for osteoporosis. In two different Cathepsin K inhibitors, <scene name='Papain/Cathkaldinhibit/1'>an aldehyde inhibitor</scene>, [[1BP4]], and <scene name='Papain/Cathkketoinhibition/2'>a keto inhibitor</scene>, [[1BQI]]. 1BP4, N-[(benzyloxy)carbonyl]-L-leucyl-N-[(2S)-1-hydroxy-4-methylpentan-2-yl]-L-leucinamide, inhibits by interacting with 11 different residues on papain: Gln-19, Gly-20, Ser-21, Gly-23, Asn-64, Gly-65, Gln-142, Asp-158, His-159, Trp-177, and Trp-181. These interactions range from hydrophobic, electrostatic, and hydrogen bonding, to <scene name='Papain/Cathkaldinhibitpistacking/2'>ring stacking</scene>, illustrated in blue, between the aromatic ring of the carbobenzyl group on 1BP4, and Trp-177 of papain. The inhibition of papain by IBQI, carbobenzyloxy-(L)-leucinyl-(L)leucinyl methoxymethylketone, is quite similar to that of IBP4, although it does not bind quite as tightly. It binds to seven residues of papain: Gln-19, Gly-23, Gly-65, Gln-142, His-159, Trp-177, Trp-181. Additionally, it has similar <scene name='Papain/Cathkketoinhibitionringstackin/3'>ring stacking</scene>, shown in blue, between the Cbz ring on the inhibitor and Trp-177.<ref> PMID:9804696 </ref>