Papain: Difference between revisions

The goal of research for the development of an inhibitor for <scene name='Papain/Cathepsin_k/1'>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, it is evident that the inhibitor binds with much closer proximity than that of Clik148. 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: Gln19, Gly20, Ser21, Gly23, Asn64, Gly65, Gln142, Asp158, His159, Trp177, and Trp181. These interactions range from hydrophobic, electrostatic, and hydrogen bonding, to <scene name='Papain/Cathkaldinhibitpistacking/1'>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: Gln19, Gly23, Gly65, Gln142, His159, Trp177, Trp181. Additionally, it has similar <scene name='Papain/Cathkketoinhibitionringstackin/1'>ring stacking</scene>, shown in blue, between the Cbz ring on the inhibitor and Trp 177, though it is more difficult to visualize with the given PDB file.<ref> PMID:9804696 </ref>  

'''Cathepsin L''' is another inhibitor of the papain enzyme.  <scene name='Papain/Cathepsin_l/1'>Cathepsin L</scene> interacts with the <scene name='Papain/Cathepsin_l_interaction_w_pap/1'>Papain residues</scene> Gln19, Cys25, Gly66, Asp158, and Trp177 by hydrogen bonding them (Cathepsin L is illustrated in CPK coloring while the interacting sites of Papain are also shown in CPK. In addition to hydrogen bonding, hydrophobic interactions exist to exclude water, allowing the papain enzyme and Cathepsin L to associate even closer.  Finally, <scene name='Papain/Stacking_cathl/1'>Ring Stacking</scene> between Trp177 and the Capthespin L molecule hold them tightly together.<ref>PMID:18598021</ref> Cathepsin L plays a roll in many different diseases including malaria, leishmaniasis, Chagas' disease, African trypanosomiasis, toxoplasmosis, and amoebiasis. Some studies show that there is a relation between cathepsins and certain cancers, alzheimer's, and arthritis. <ref> PMID:20920298 </ref>