Tobacco Etch Virus (TEV) Protease

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==Structure of TEV Protease==
==Structure of TEV Protease==
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TEV protease is classified as an all β protein which adopts a <scene name='User:Ashley_Steere/Sandbox_1/2_domains/1'>two-domain</scene> antiparallel β-barrel fold, typical of trypsin-like serine proteases, where the β sheet in the first domain folds to form an antiparallel <scene name='Tobacco_Etch_Virus_(TEV)_Protease/Beta_barrel/1'>β-barrel</scene> (<span style="color:cyan;background-color:black;font-weight:bold;">cyan</span> and the β sheet in the second domain is open (<font color='red'><b>red</b></font>). Like typical serine proteases, the β-barrel contains a <scene name='Tobacco_Etch_Virus_(TEV)_Protease/Greek_key/1'>Greek key</scene> motif. Located at the interface between the two domains is the <scene name='Tobacco_Etch_Virus_(TEV)_Protease/Active_site/1'>catalytic triad</scene>, composed of His46, Asp81, and Cys151. A structural comparison with related proteins reveals that the TEV protease fold is most similar to that of other 3C-type [http://en.wikipedia.org/wiki/Cysteine_protease cysteine proteases] from the [http://en.wikipedia.org/wiki/Picornavirus ''Picornaviridae''] virus family, such as the [http://proteopedia.org/wiki/index.php/1hav hepatitis A virus], the [http://proteopedia.org/wiki/index.php/1l1n poliovirus], the foot and mouth disease virus and [http://proteopedia.org/wiki/index.php/1cqq rhinovirus], which serve a similar function as the TEV protease in their respective viruses. However, although the overall fold of TEV protease and these related proteins is indeed very similar, the actual atomic coordinates are very different, with the root mean square deviation for α carbons between 2.4 to 3.5 Å <ref name="Phan" />.
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TEV protease is classified as an all β protein which adopts a <scene name='35/350966/2_domains/1'>two-domain</scene> antiparallel β-barrel fold, typical of trypsin-like serine proteases, where the β sheet in the first domain folds to form an antiparallel <scene name='Tobacco_Etch_Virus_(TEV)_Protease/Beta_barrel/1'>β-barrel</scene> (<span style="color:cyan;background-color:black;font-weight:bold;">cyan</span> and the β sheet in the second domain is open (<font color='red'><b>red</b></font>). Like typical serine proteases, the β-barrel contains a <scene name='Tobacco_Etch_Virus_(TEV)_Protease/Greek_key/1'>Greek key</scene> motif. Located at the interface between the two domains is the <scene name='Tobacco_Etch_Virus_(TEV)_Protease/Active_site/1'>catalytic triad</scene>, composed of His46, Asp81, and Cys151. A structural comparison with related proteins reveals that the TEV protease fold is most similar to that of other 3C-type [http://en.wikipedia.org/wiki/Cysteine_protease cysteine proteases] from the [http://en.wikipedia.org/wiki/Picornavirus ''Picornaviridae''] virus family, such as the [http://proteopedia.org/wiki/index.php/1hav hepatitis A virus], the [http://proteopedia.org/wiki/index.php/1l1n poliovirus], the foot and mouth disease virus and [http://proteopedia.org/wiki/index.php/1cqq rhinovirus], which serve a similar function as the TEV protease in their respective viruses. However, although the overall fold of TEV protease and these related proteins is indeed very similar, the actual atomic coordinates are very different, with the root mean square deviation for α carbons between 2.4 to 3.5 Å <ref name="Phan" />.
==Classification==
==Classification==

Revision as of 08:38, 27 June 2017

TEV protease catalytic domain (grey) complex with polypeptide substrate (pink) and acetate, 1lvm

Drag the structure with the mouse to rotate

3D structures of TEV protease

1q31 – TEV (mutant) – Tobacco etch virus
1lvb, 1lvm – TEV catalytic domain (mutant) + oligopeptide substrate

Additional Resources

For additional information, See: Viral Infections

References

  1. Ryan MD, Flint M. Virus-encoded proteinases of the picornavirus super-group. J Gen Virol. 1997 Apr;78 ( Pt 4):699-723. PMID:9129643
  2. Stanway G. Structure, function and evolution of picornaviruses. J Gen Virol. 1990 Nov;71 ( Pt 11):2483-501. PMID:2254747
  3. 3.0 3.1 3.2 3.3 3.4 3.5 3.6 3.7 Phan J, Zdanov A, Evdokimov AG, Tropea JE, Peters HK 3rd, Kapust RB, Li M, Wlodawer A, Waugh DS. Structural basis for the substrate specificity of tobacco etch virus protease. J Biol Chem. 2002 Dec 27;277(52):50564-72. Epub 2002 Oct 10. PMID:12377789 doi:http://dx.doi.org/10.1074/jbc.M207224200
  4. 4.0 4.1 Yin J, Niu C, Cherney MM, Zhang J, Huitema C, Eltis LD, Vederas JC, James MN. A mechanistic view of enzyme inhibition and peptide hydrolysis in the active site of the SARS-CoV 3C-like peptidase. J Mol Biol. 2007 Aug 24;371(4):1060-74. Epub 2007 Jun 8. PMID:17599357 doi:10.1016/j.jmb.2007.06.001
  5. Arad D, Kreisberg R, Shokhen M. Structural and mechanistic aspects of 3C proteases from the Picornavirus family. J Chem Inf Comput Sci. 1993 May-Jun;33(3):345-9. PMID:8320292
  6. Cleland WW, Frey PA, Gerlt JA. The low barrier hydrogen bond in enzymatic catalysis. J Biol Chem. 1998 Oct 2;273(40):25529-32. PMID:9748211
  7. 7.0 7.1 Cassidy CS, Lin J, Frey PA. A new concept for the mechanism of action of chymotrypsin: the role of the low-barrier hydrogen bond. Biochemistry. 1997 Apr 15;36(15):4576-84. PMID:9109667 doi:10.1021/bi962013o
  8. 8.0 8.1 8.2 Kapust RB, Tozser J, Copeland TD, Waugh DS. The P1' specificity of tobacco etch virus protease. Biochem Biophys Res Commun. 2002 Jun 28;294(5):949-55. PMID:12074568 doi:10.1016/S0006-291X(02)00574-0
  9. 9.0 9.1 Nunn CM, Jeeves M, Cliff MJ, Urquhart GT, George RR, Chao LH, Tscuchia Y, Djordjevic S. Crystal structure of tobacco etch virus protease shows the protein C terminus bound within the active site. J Mol Biol. 2005 Jul 1;350(1):145-55. PMID:15919091 doi:10.1016/j.jmb.2005.04.013
  10. Mohanty AK, Simmons CR, Wiener MC. Inhibition of tobacco etch virus protease activity by detergents. Protein Expr Purif. 2003 Jan;27(1):109-14. PMID:12509992
  11. Kapust RB, Tozser J, Fox JD, Anderson DE, Cherry S, Copeland TD, Waugh DS. Tobacco etch virus protease: mechanism of autolysis and rational design of stable mutants with wild-type catalytic proficiency. Protein Eng. 2001 Dec;14(12):993-1000. PMID:11809930
  12. Gorbalenya AE, Blinov VM, Donchenko AP. Poliovirus-encoded proteinase 3C: a possible evolutionary link between cellular serine and cysteine proteinase families. FEBS Lett. 1986 Jan 6;194(2):253-7. PMID:3000829
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