Papain: Difference between revisions

'''Papain'''. Meat tenderizer. Old time home remedy for insect, jellyfish, and stingray stings<ref>[http://www.ameriden.com/products/advanced-digestive-enzyme/] Ameridan International</ref>. Who would have thought that a sulfhydryl protease from the latex of the papaya fruit, ''Carica papaya'' and ''Vasconcellea cundinamarcensis'', would have such a practical application beyond Proteopedia?

Papain is a 23.4 kDa, 212 residue cysteine protease, also known as '''papaya proteinase I''', from the peptidase C1 family ([[EC Number|E.C.]] [[Hydrolase|3.4.22.2]]).<ref>[http://www.uniprot.org/uniprot/P00784] Uniprot</ref><ref name="9PAP PDB">[http://www.pdb.org/pdb/explore/explore.do?structureId=9PAP] 9PAP PDB</ref> It is the natural product of the [http://en.wikipedia.org/wiki/Carica_papaya Papaya](''Carica papaya'')<ref name="Sigma Aldrich">[http://www.sigmaaldrich.com/life-science/metabolomics/enzyme-explorer/analytical-enzymes/papain.html] Sigma Aldrich</ref>, and may be extracted from the plant's latex, leaves and roots. Papain displays a broad range of functions, acting as an endopeptidase, exopeptidase, amidase, and esterase,<ref name="Worthington">[http://www.worthington-biochem.com/pap/default.html] Worthington</ref> with its optimal activity values for pH lying between 6.0 and 7.0, and its optimal temperature for activity is 65 °C. Its pI values are 8.75 and 9.55, and it is best visualized at a wavelength of 278 nm. <ref name="Sigma Aldrich" />

Papain's enzymatic use was first discovered in 1873 by G.C. Roy who published his results in the Calcutta Medical Journal in the article, "The Solvent Action of Papaya Juice on Nitrogenous Articles of Food." In 1879, Papain was named officially by Wurtz and Bouchut, who managed to partially purify the product from the sap of papaya. It wasn't until the mid-twentieth century that the complete purification and isolation of Papain was achieved. In 1968, Drenth et al. determined the structure of Papain by [[X-ray crystallography|x-ray crystallography]], making it the second enzyme whose structure was successfully determined by x-ray crystallography. Additionally, Papain was the first cysteine protease to have its structure identified.<ref name="Worthington" /> In 1984, Kamphuis et al. determined the geometry of the active site, and the three-dimensional structure was visualized to a 1.65 Angstrom solution.<ref name="Structure">PMID:6502713</ref> Today, studies continue on the stability of Papain, involving changes in environmental conditions as well as testing of inhibitors such as phenylmethanesulfonylfluoride (PMSF), TLCK, TPCK, aplh2-macroglobulin, heavy metals, AEBSF, antipain, cystatin, E-64, leupeptin, sulfhydryl binding agents, carbonyl reagents, and alkylating agents.<ref name="Worthington" />

==Structure==

There are a small number of <scene name='Papain/Stefin_b_hbonds/2'>direct hydrogen bonds</scene> (labeled in <scene name='Papain/Stefin_b_hbonds/1'>this scene</scene>, between Stefin B and Papain, however there are many more polar interactions mediated by <scene name='Papain/Stfn_b_solvent_intrxns/1'>solvent bridges</scene>, the solvent being mainly <big><b><font color='darkturquoise'>water</font></b></big>.  Thirteen solvent molecules of water bridge polar residues of the enzyme and inhibitor.  Seventeen hydrogen bonds are made with a solvent molecule and Stefin B.  Fourteen of these bridges form a Papain contact.  The rest of the interactions are largely hydrophobic-- involving apolar <scene name='Papain/Stefin_b_vdw/2'>Van der Waals forces</scene>.<ref> PMID:2347312 </ref>

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==3D structures of papain==

{{#tree:id=OrganizedByTopic|openlevels=0|

**[[1khp]], [[1khq]] - PAP + peptide inhibitor<br />

**[[1ppd]] – hydroxyethyl-thioPAP<br />

*Papain complex with protein inhibitor

**[[3e1z]] - PAP + chagasin<br />

**[[3ima]] - PAP + tarocystatin

}}