Papain: Difference between revisions

==='''Leupeptin'''===

<scene name='Papain/Leupeptin/4'>Leupeptin</scene> is a commonly studied broad-spectrum competitive protease inhibitor first crystallized by Schröder et. al.  It inhibits by binding and interacting with the active site which allows it to block the enzyme's desired protein substrate from binding.  There are many <scene name='Papain/Leupeptin_residues/4'>ligand contacts</scene> that interact with leupeptin, which predominantly interact <scene name='Papain/1pop_sam_leupeptin_hydrophobic/4'>hydrophobically</scene> (interactions in blue), including tyrosine, tryptophan, and valine, which coordinate the bound leuptin. Some of the enzyme's residues also make <scene name='Papain/Leupeptin_hbonds/2'>hydrogen bonds</scene>.  These hydrogen bonds, shown in white, include interactions between hydrogens on both Gln-19 and the amide nitrogen of the catalytic Cys-25 with the arginal carbanion, forming the catalytically important oxyanion hole.  In addition, Gly-66 interacts with the second leucine in leupeptin while Asp-158 interacts with a hydrogen on the arginal.  These interactions further stabilize and orient the substrate in the binding pocket<ref name="Schroder">[http://www.sciencedirect.com/science/article/pii/001457939381128M] Schröder, E., C. Phillips, E. Garman, K. Harlos, C. Crawford. 1997. X-ray crystallographic structure of a papain-leupeptin complex. FEBS Letters 315: 38-42</ref>.

==='''Cathepsin K'''===

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>  

<scene name='Papain/Cathepsin_l/1'>Cathepsin L</scene>, another inhibitor of Papain, is an endosomal cysteine protease that is believed to have both physiological and pathophysiological effects on the human body. It has been indicated not only in cancer, rhematoid  and osteo arthritis, and Alzheimer's, but its mechanism also appears similar to that of Ebola, SARS, Leishmania, malaria, Chagas' disease, African trypanosomiasis, toxoplasmosis, and amoebiasis.<ref> PMID:20920298 </ref>  Understanding the mechanism of inhibition through the use of papain is therefore crucial to developing treatments for such diseases.<ref> PMID:18499453 </ref> Cathepsin L interacts with the <scene name='Papain/Cathepsin_l_interaction_w_pap/2'>residues</scene> Gln-19, Cys-25, Gly-66, Asp-158, and Trp-177 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.   

==='''Stefin B'''===

</StructureSection>

==Common Uses==

A recent New York Times article featured papain and other digestive enzymes. With the number of individuals suffering from irritable bowel syndrome and other gastrointestinal issues, many people are turning toward natural digestive aid supplements like papain.  The author even talks about the use of papain along with a pineapple enzyme, bromelain, in cosmetic facial masks.  Dr. Adam R. Kolker (a plastic surgeon) is quoted in the article saying that "For skin that is sensitive, enzymes are wonderful."  He bases these claims off the idea that proteases like papain help to break peptide bonds holding dead skin cells to the live skin cells.<ref> [http://www.nytimes.com/2012/02/23/fashion/enzymes-once-sidelined-try-to-grab-the-spotlight.html] Enzymes Try to Grab the Spotlight </ref>

===Commercial and Biomedical===

Papain digests most proteins, often more extensively than pancreatic proteases. It has a very broad specificity and is known to cleave peptide bonds of basic amino acids and leucine and glycine residues, but prefers amino acids with large hydrophobic side chains. This non-specific nature of papain's hydrolase activity has led to its use in many and varied commercial products.  It is often used as a meat tenderizer because it can hydrolyze the peptide bonds of collagen, elastin, and actomyosin.  It is also used in contact lens solution to remove protein deposits on the lenses and marketed as a digestive supplement.  <ref name="Web MD">  Finally, papain has several common uses in general biomedical research, including a gentle cell isolation agent, production of glycopeptides from purified proteoglycans, and solubilization of integral membrane proteins.  It is also notable for its ability to specifically cleave IgG and IgM antibodies above and below the disulfide bonds that join the heavy chains and that is found between the light chain and heavy chain. This generates two monovalent Fab segments, that each have a single antibody binding sites, and an intact Fc fragment.<ref name="Worthington" />  

==Fun Trivia==

Remember the 2002 SARS (Severe Acute Respiratory Syndrome) epidemic that placed global health, particularly in Southeast Asia, in a precarious state? On-going research is happening to further understand the mechanisms of this coronavirus, so that future steps can be taken for prevention. Its been found that the replication of RNA for this virus is mediated by two viral proteases that have many papain-like characteristics. <ref>PMID: 16306590 </ref>   

==References==