1z8r
From Proteopedia
(New page: 200px<br /><applet load="1z8r" size="450" color="white" frame="true" align="right" spinBox="true" caption="1z8r" /> '''2A cysteine proteinase from human coxsackiev...) |
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| - | [[Image:1z8r.gif|left|200px]]<br /><applet load="1z8r" size=" | + | [[Image:1z8r.gif|left|200px]]<br /><applet load="1z8r" size="350" color="white" frame="true" align="right" spinBox="true" |
caption="1z8r" /> | caption="1z8r" /> | ||
'''2A cysteine proteinase from human coxsackievirus B4 (strain JVB / Benschoten / New York / 51)'''<br /> | '''2A cysteine proteinase from human coxsackievirus B4 (strain JVB / Benschoten / New York / 51)'''<br /> | ||
==Overview== | ==Overview== | ||
| - | The 2A proteinases (2A(pro)) from the picornavirus family are | + | The 2A proteinases (2A(pro)) from the picornavirus family are multifunctional cysteine proteinases that perform essential roles during viral replication, involving viral polyprotein self-processing and shutting down host cell protein synthesis through cleavage of the eukaryotic initiation factor 4G (eIF4G) proteins. Coxsackievirus B4 (CVB4) 2A(pro) also cleaves heart muscle dystrophin, leading to cytoskeletal dysfunction and the symptoms of human acquired dilated cardiomyopathy. We have determined the solution structure of CVB4 2A(pro) (extending in an N-terminal direction to include the C-terminal eight residues of CVB4 VP1, which completes the VP1-2A(pro) substrate region). In terms of overall fold, it is similar to the crystal structure of the mature human rhinovirus serotype 2 (HRV2) 2A(pro), but the relatively low level (40%) of sequence identity leads to a substantially different surface. We show that differences in the cI-to-eI2 loop between HRV2 and CVB4 2A(pro) translate to differences in the mechanism of eIF4GI recognition. Additionally, the nuclear magnetic resonance relaxation properties of CVB4 2A(pro), particularly of residues G1 to S7, F64 to S67, and P107 to G111, reveal that the substrate region is exchanging in and out of a conformation in which it occupies the active site with association and dissociation rates in the range of 100 to 1,000 s(-1). This exchange influences the conformation of the active site and points to a mechanism for how self-processing can occur efficiently while product inhibition is avoided. |
==About this Structure== | ==About this Structure== | ||
| - | 1Z8R is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Human_coxsackievirus_b1 Human coxsackievirus b1] with ZN as [http://en.wikipedia.org/wiki/ligand ligand]. Active as [http://en.wikipedia.org/wiki/Picornain_2A Picornain 2A], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.4.22.29 3.4.22.29] Full crystallographic information is available from [http:// | + | 1Z8R is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Human_coxsackievirus_b1 Human coxsackievirus b1] with <scene name='pdbligand=ZN:'>ZN</scene> as [http://en.wikipedia.org/wiki/ligand ligand]. Active as [http://en.wikipedia.org/wiki/Picornain_2A Picornain 2A], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.4.22.29 3.4.22.29] Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1Z8R OCA]. |
==Reference== | ==Reference== | ||
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[[Category: Picornain 2A]] | [[Category: Picornain 2A]] | ||
[[Category: Single protein]] | [[Category: Single protein]] | ||
| - | [[Category: Baxter, N | + | [[Category: Baxter, N J.]] |
| - | [[Category: Hounslow, A | + | [[Category: Hounslow, A M.]] |
| - | [[Category: Liebig, H | + | [[Category: Liebig, H D.]] |
[[Category: Roetzer, A.]] | [[Category: Roetzer, A.]] | ||
| - | [[Category: Sedelnikova, S | + | [[Category: Sedelnikova, S E.]] |
[[Category: Skern, T.]] | [[Category: Skern, T.]] | ||
| - | [[Category: Waltho, J | + | [[Category: Waltho, J P.]] |
[[Category: ZN]] | [[Category: ZN]] | ||
[[Category: beta barrel coordinated zinc ion]] | [[Category: beta barrel coordinated zinc ion]] | ||
| - | ''Page seeded by [http:// | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 16:13:13 2008'' |
Revision as of 14:13, 21 February 2008
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2A cysteine proteinase from human coxsackievirus B4 (strain JVB / Benschoten / New York / 51)
Overview
The 2A proteinases (2A(pro)) from the picornavirus family are multifunctional cysteine proteinases that perform essential roles during viral replication, involving viral polyprotein self-processing and shutting down host cell protein synthesis through cleavage of the eukaryotic initiation factor 4G (eIF4G) proteins. Coxsackievirus B4 (CVB4) 2A(pro) also cleaves heart muscle dystrophin, leading to cytoskeletal dysfunction and the symptoms of human acquired dilated cardiomyopathy. We have determined the solution structure of CVB4 2A(pro) (extending in an N-terminal direction to include the C-terminal eight residues of CVB4 VP1, which completes the VP1-2A(pro) substrate region). In terms of overall fold, it is similar to the crystal structure of the mature human rhinovirus serotype 2 (HRV2) 2A(pro), but the relatively low level (40%) of sequence identity leads to a substantially different surface. We show that differences in the cI-to-eI2 loop between HRV2 and CVB4 2A(pro) translate to differences in the mechanism of eIF4GI recognition. Additionally, the nuclear magnetic resonance relaxation properties of CVB4 2A(pro), particularly of residues G1 to S7, F64 to S67, and P107 to G111, reveal that the substrate region is exchanging in and out of a conformation in which it occupies the active site with association and dissociation rates in the range of 100 to 1,000 s(-1). This exchange influences the conformation of the active site and points to a mechanism for how self-processing can occur efficiently while product inhibition is avoided.
About this Structure
1Z8R is a Single protein structure of sequence from Human coxsackievirus b1 with as ligand. Active as Picornain 2A, with EC number 3.4.22.29 Full crystallographic information is available from OCA.
Reference
Structure and dynamics of coxsackievirus B4 2A proteinase, an enyzme involved in the etiology of heart disease., Baxter NJ, Roetzer A, Liebig HD, Sedelnikova SE, Hounslow AM, Skern T, Waltho JP, J Virol. 2006 Feb;80(3):1451-62. PMID:16415022
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