1m72: Difference between revisions

Revision as of 14:52, 21 February 2008

Crystal Structure of Caspase-1 from Spodoptera frugiperda

OverviewOverview

Caspases play an essential role in the execution of apoptosis. These cysteine proteases are highly conserved among metazoans and are translated as inactive zymogens, which are activated by proteolytic cleavages to generate the large and small subunits and remove the N-terminal prodomain. The 2.3 A resolution crystal structure of active Sf-caspase-1, the principal effector caspase of the insect Spodoptera frugiperda, is presented here. The structure represents the first nonhuman caspase to be resolved. The structure of the cleaved and active protease was determined with the tetrapeptide inhibitor N-acetyl-Asp-Glu-Val-Asp-chloromethylketone covalently bonded to the active site cysteine. As expected, the overall fold of Sf-caspase-1 is exceedingly similar to that of the five active caspases from humans solved to date. The overall structure and active site arrangement of Sf-caspase-1 is most comparable with that of the human effector caspases, with which it shares highest sequence homology. The most prominent structural difference with Sf-caspase-1 is the position of the N-terminal region of the large subunit. Unlike the N terminus of human caspases, the N terminus of Sf-caspase-1 originates from the active site side where it interacts with active site loop L2 and then extends to the backside of the heterodimer. This unusual structural arrangement raises the possibility that the N-terminal prodomain plays a regulatory role during effector caspase activation or enzyme activity in insects.

About this StructureAbout this Structure

1M72 is a Single protein structure of sequence from Spodoptera frugiperda with and as ligands. Active as Caspase-1, with EC number 3.4.22.36 Full crystallographic information is available from OCA.

ReferenceReference

Crystal structure of an invertebrate caspase., Forsyth CM, Lemongello D, LaCount DJ, Friesen PD, Fisher AJ, J Biol Chem. 2004 Feb 20;279(8):7001-8. Epub 2003 Nov 27. PMID:14645217

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-[[Image:1m72.gif|left|200px]]<br /><applet load="1m72" size="450" color="white" frame="true" align="right" spinBox="true"
+[[Image:1m72.gif|left|200px]]<br /><applet load="1m72" size="350" color="white" frame="true" align="right" spinBox="true"
 caption="1m72, resolution 2.30&Aring;" />
 '''Crystal Structure of Caspase-1 from Spodoptera frugiperda'''<br />
 ==Overview==
-Caspases play an essential role in the execution of apoptosis. These, cysteine proteases are highly conserved among metazoans and are translated, as inactive zymogens, which are activated by proteolytic cleavages to, generate the large and small subunits and remove the N-terminal prodomain., The 2.3 A resolution crystal structure of active Sf-caspase-1, the, principal effector caspase of the insect Spodoptera frugiperda, is, presented here. The structure represents the first nonhuman caspase to be, resolved. The structure of the cleaved and active protease was determined, with the tetrapeptide inhibitor, N-acetyl-Asp-Glu-Val-Asp-chloromethylketone covalently bonded to the, active site cysteine. As expected, the overall fold of Sf-caspase-1 is, exceedingly similar to that of the five active caspases from humans solved, to date. The overall structure and active site arrangement of Sf-caspase-1, is most comparable with that of the human effector caspases, with which it, shares highest sequence homology. The most prominent structural difference, with Sf-caspase-1 is the position of the N-terminal region of the large, subunit. Unlike the N terminus of human caspases, the N terminus of, Sf-caspase-1 originates from the active site side where it interacts with, active site loop L2 and then extends to the backside of the heterodimer., This unusual structural arrangement raises the possibility that the, N-terminal prodomain plays a regulatory role during effector caspase, activation or enzyme activity in insects.
+Caspases play an essential role in the execution of apoptosis. These cysteine proteases are highly conserved among metazoans and are translated as inactive zymogens, which are activated by proteolytic cleavages to generate the large and small subunits and remove the N-terminal prodomain. The 2.3 A resolution crystal structure of active Sf-caspase-1, the principal effector caspase of the insect Spodoptera frugiperda, is presented here. The structure represents the first nonhuman caspase to be resolved. The structure of the cleaved and active protease was determined with the tetrapeptide inhibitor N-acetyl-Asp-Glu-Val-Asp-chloromethylketone covalently bonded to the active site cysteine. As expected, the overall fold of Sf-caspase-1 is exceedingly similar to that of the five active caspases from humans solved to date. The overall structure and active site arrangement of Sf-caspase-1 is most comparable with that of the human effector caspases, with which it shares highest sequence homology. The most prominent structural difference with Sf-caspase-1 is the position of the N-terminal region of the large subunit. Unlike the N terminus of human caspases, the N terminus of Sf-caspase-1 originates from the active site side where it interacts with active site loop L2 and then extends to the backside of the heterodimer. This unusual structural arrangement raises the possibility that the N-terminal prodomain plays a regulatory role during effector caspase activation or enzyme activity in insects.
 ==About this Structure==
-M72 is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Spodoptera_frugiperda Spodoptera frugiperda] with ACE and EDO as [http://en.wikipedia.org/wiki/ligands ligands]. Active as [http://en.wikipedia.org/wiki/Caspase-1 Caspase-1], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.4.22.36 3.4.22.36] Full crystallographic information is available from [http://ispc.weizmann.ac.il/oca-bin/ocashort?id=1M72 OCA].
+M72 is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Spodoptera_frugiperda Spodoptera frugiperda] with <scene name='pdbligand=ACE:'>ACE</scene> and <scene name='pdbligand=EDO:'>EDO</scene> as [http://en.wikipedia.org/wiki/ligands ligands]. Active as [http://en.wikipedia.org/wiki/Caspase-1 Caspase-1], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.4.22.36 3.4.22.36] Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1M72 OCA].
 ==Reference==
@@ Line 14: / Line 14: @@
 [[Category: Single protein]]
 [[Category: Spodoptera frugiperda]]
-[[Category: Fisher, A.J.]]
+[[Category: Fisher, A J.]]
-[[Category: Forsyth, C.M.]]
+[[Category: Forsyth, C M.]]
-[[Category: Friesen, P.D.]]
+[[Category: Friesen, P D.]]
 [[Category: Lemongello, D.]]
 [[Category: ACE]]
@@ Line 23: / Line 23: @@
 [[Category: cysteine protease]]
-''Page seeded by [http://ispc.weizmann.ac.il/oca OCA ] on Tue Nov 20 21:11:49 2007''
+''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 13:52:10 2008''