Sandbox 35

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==Structure==
==Structure==
Papain's polypeptide chain consists of 212 amino acid residues which fold to form a groove containing the active site between its two domains. Its
Papain's polypeptide chain consists of 212 amino acid residues which fold to form a groove containing the active site between its two domains. Its
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<scene name='Sandbox_35/Secondary_structure_papain/2'>secondary structure</scene> consists of 17 <scene name='Sandbox_35/2nd_struc_papain_beta/2'>beta sheet</scene> strands and 7 <scene name='Sandbox_35/2nd_struc_papain_helix/2'>alpha helices</scene> giving it a composition 21% and 25% respectively. <ref name="9PAP PDB">[http://www.pdb.org/pdb/explore/explore.do?structureId=9PAP]9PAP PDB</ref>. The hydrogen bonds within the alpha helices are shorter than the typical alpha helix because of C=O being directed further away from the helical axis. Moreover, the beta sheet hydrogen bonding constraints and structural angles show great variation; hydrogen bonds in the sheets central tend to be shorter than on the fringes. Three disulfide bonds (yellow) serve to further hold papain's structure together.
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<scene name='Sandbox_35/Secondary_structure_papain/2'>secondary structure</scene> consists of 17 <scene name='Sandbox_35/2nd_struc_papain_beta/2'>beta sheet</scene> strands and 7 <scene name='Sandbox_35/2nd_struc_papain_helix/2'>alpha helices</scene> giving it a composition 21% and 25% respectively. <ref name="9PAP PDB">[http://www.pdb.org/pdb/explore/explore.do?structureId=9PAP]9PAP PDB</ref> The hydrogen bonds within the alpha helices are shorter than the typical alpha helix because of C=O being directed further away from the helical axis. Moreover, the beta sheet hydrogen bonding constraints and structural angles show great variation; hydrogen bonds in the sheets central tend to be shorter than on the fringes. Three disulfide bonds (yellow) serve to hold papain's tertiary structure together.
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The <scene name='Sandbox_35/Active_site_papain/3'>active site</scene> consists of <ref>PMID: 8140097</ref>
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The <scene name='Sandbox_35/Active_site_papain/3'>active site</scene> primarily consist of three main residues Cys25-His159-Asn175 that resemble the catalytic triad of chymotrypsin <ref>PMID: 8140097</ref><ref>PMID: 2397208</ref>
<scene name='Sandbox_35/Active_site_asp_158_papain/1'>Asp 158</scene>
<scene name='Sandbox_35/Active_site_asp_158_papain/1'>Asp 158</scene>
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Crystallization of the protease under conditions of 62% (w/w) methanol in water reveals water playing a crucial role in providing structural stability. The 21 internal water molecules surrounding adjacent papain molecules appear to form an encasement that limit protein to protein interaction <ref>PMID: 6502713</ref>.
===Distribution of Residues===
===Distribution of Residues===
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Papain has a scattered distribution of <scene name='Sandbox_35/Papain_acid_and_basic_residues/1'>acidic and basic residues</scene>, but can be seen to have more basic residues than acidic shedding light into the application of its use as a digestive supplement. <ref>[http://www.webmd.com/vitamins-supplements/ingredientmono-69-PAPAIN.aspx?activeIngredientId=69&activeIngredientName=PAPAIN] WebMD</ref> Its <scene name='Sandbox_35/Hydrophobicity_papain/3'>polar and non-polar residues</scene> build on this picture with <scene name='Sandbox_35/Papain_polar/1'>polar residues</scene> resting more on the outside and <scene name='Sandbox_35/Nonpolar_papain/2'>non-polar residues</scene> sequestering near the center. Observations have revealed that the proteins atomic positions are more ordered going from the center out <ref>PMID: 6502713 </ref>
+
Papain has a scattered distribution of <scene name='Sandbox_35/Papain_acid_and_basic_residues/1'>acidic and basic residues</scene>, but can be seen to have more basic residues than acidic shedding light into the application of its use as a digestive supplement. <ref>[http://www.webmd.com/vitamins-supplements/ingredientmono-69-PAPAIN.aspx?activeIngredientId=69&activeIngredientName=PAPAIN] WebMD</ref> Its <scene name='Sandbox_35/Hydrophobicity_papain/3'>polar and non-polar residues</scene> build on this picture with <scene name='Sandbox_35/Papain_polar/1'>polar residues</scene> resting more on the outside and <scene name='Sandbox_35/Nonpolar_papain/2'>non-polar residues</scene> sequestering near the center. Observations have revealed that the proteins atomic positions are more ordered going from the center toward the outside <ref>PMID: 6502713 </ref>
===Ligands interactions===
===Ligands interactions===

Revision as of 00:01, 14 November 2011

Please do NOT make changes to this Sandbox. Sandboxes 30-60 are reserved for use by Biochemistry 410 & 412 at Messiah College taught by Dr. Hannah Tims during Fall 2012 and Spring 2013.


Contents

Papain

Introduction

Cartoon Peak at Pepsin
Cartoon Peak at Pepsin

DID YOU KNOW?

. Meat tenderizer. Old time home remedy for insect, jellyfish, and stingray stings[1]. 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?


This protease belongs to an extended family of aminopeptidases, dipeptidyl peptidases, endopeptidases, and other enzymes having both exo- and endo-peptidase activity. The inactivated zymogen with N-terminal propeptide regions - providing stability in alkaline environments and enabling proper folding - is activated through removal of the propeptide regions [2][3].

Structure of Papain (PDB entry 9PAP)

Drag the structure with the mouse to rotate

Catalytic Mechanism

General mechanism of papain catalysis.
General mechanism of papain catalysis[10].

References

  1. ↑ [1] Ameridan International
  2. ↑ Rawlings ND, Barrett AJ. Families of cysteine peptidases. Methods Enzymol. 1994;244:461-86. PMID:7845226
  3. ↑ Yamamoto Y, Kurata M, Watabe S, Murakami R, Takahashi SY. Novel cysteine proteinase inhibitors homologous to the proregions of cysteine proteinases. Curr Protein Pept Sci. 2002 Apr;3(2):231-8. PMID:12188906
  4. ↑ [2]9PAP PDB
  5. ↑ Wang J, Xiang YF, Lim C. The double catalytic triad, Cys25-His159-Asp158 and Cys25-His159-Asn175, in papain catalysis: role of Asp158 and Asn175. Protein Eng. 1994 Jan;7(1):75-82. PMID:8140097
  6. ↑ Ménard R, Khouri HE, Plouffe C, Dupras R, Ripoll D, Vernet T, Tessier DC, Lalberté F, Thomas DY, Storer AC. A protein engineering study of the role of aspartate 158 in the catalytic mechanism of papain. Biochemistry. 1990 Jul 17;29(28):6706-13. PMID:2397208 doi:10.1021/bi00480a021
  7. ↑ Kamphuis IG, Kalk KH, Swarte MB, Drenth J. Structure of papain refined at 1.65 A resolution. J Mol Biol. 1984 Oct 25;179(2):233-56. PMID:6502713
  8. ↑ [3] WebMD
  9. ↑ Kamphuis IG, Kalk KH, Swarte MB, Drenth J. Structure of papain refined at 1.65 A resolution. J Mol Biol. 1984 Oct 25;179(2):233-56. PMID:6502713
  10. ↑ [4] University of Maine


http://www.pdb.org/pdb/explore/explore.do?structureId=2PAD • Show the secondary structures. • Compare the distribution of polar residues to that of nonpolar residues. • Highlight the active site. • If you can find a PDB file of the enzyme that contains a pseudo-substrate (may be inhibitor), highlight it. • Show the contacts or attractions that are present between the pseudo-substrate and the protein, and if the enzyme has multiple subunits, show the contacts between the subunits. • Identify any other ligands that are present in the structure and the types of contacts that are present between them and the protein

http://proteopedia.org/wiki/index.php/Sandbox_55#cite_note-18 Table of contents Pictures References (cross links)

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