1nx0: Difference between revisions

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Structure of Calpain Domain 6 in Complex with Calpastatin DIC

OverviewOverview

The Ca(2+)-dependent cysteine protease calpain along with its endogenous inhibitor calpastatin is widely distributed. The interactions between calpain and calpastatin have been studied to better understand the nature of calpain inhibition by calpastatin, which can aid the design of small molecule inhibitors to calpain. Here we present the crystal structure of a complex between a calpastatin peptide and the calcium-binding domain VI of calpain. DIC19 is a 19 residue peptide, which corresponds to one of the three interacting domains of calpastatin, which is known to interact with domain VI of calpain. We present two crystal structures of DIC19 bound to domain VI of calpain, determined by molecular replacement methods to 2.5A and 2.2A resolution. In the process of crystallizing the inhibitor complex, a new native crystal form was identified which had the homodimer 2-fold axis along a crystallographic axis as opposed to the previously observed dimer in the asymmetric unit. The crystal structures of the native domain VI and its inhibitor PD150606 (3-(4-iodophenyl)-2-mercapto-(Z)-2-propenoic acid) complex were determined with the help of molecular replacement methods to 2.0A and 2.3A resolution, respectively. In addition, we built a homology model for the complex between domain IV and DIA19 peptide of calpastatin. Finally, we present a model for the calpastatin-inhibited calpain.

About this StructureAbout this Structure

1NX0 is a Protein complex structure of sequences from Sus scrofa with as ligand. Active as Hydrolase, with EC number and 3.4.22.53 3.4.22.52 and 3.4.22.53 Full crystallographic information is available from OCA.

ReferenceReference

A structural model for the inhibition of calpain by calpastatin: crystal structures of the native domain VI of calpain and its complexes with calpastatin peptide and a small molecule inhibitor., Todd B, Moore D, Deivanayagam CC, Lin GD, Chattopadhyay D, Maki M, Wang KK, Narayana SV, J Mol Biol. 2003 Apr 18;328(1):131-46. PMID:12684003

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OCA

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-[[Image:1nx0.jpg|left|200px]]<br /><applet load="1nx0" size="450" color="white" frame="true" align="right" spinBox="true"
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 caption="1nx0, resolution 2.3&Aring;" />
 '''Structure of Calpain Domain 6 in Complex with Calpastatin DIC'''<br />
 ==Overview==
-The Ca(2+)-dependent cysteine protease calpain along with its endogenous, inhibitor calpastatin is widely distributed. The interactions between, calpain and calpastatin have been studied to better understand the nature, of calpain inhibition by calpastatin, which can aid the design of small, molecule inhibitors to calpain. Here we present the crystal structure of a, complex between a calpastatin peptide and the calcium-binding domain VI of, calpain. DIC19 is a 19 residue peptide, which corresponds to one of the, three interacting domains of calpastatin, which is known to interact with, domain VI of calpain. We present two crystal structures of DIC19 bound to, domain VI of calpain, determined by molecular replacement methods to 2.5A, and 2.2A resolution. In the process of crystallizing the inhibitor, complex, a new native crystal form was identified which had the homodimer, 2-fold axis along a crystallographic axis as opposed to the previously, observed dimer in the asymmetric unit. The crystal structures of the, native domain VI and its inhibitor PD150606, (3-(4-iodophenyl)-2-mercapto-(Z)-2-propenoic acid) complex were determined, with the help of molecular replacement methods to 2.0A and 2.3A, resolution, respectively. In addition, we built a homology model for the, complex between domain IV and DIA19 peptide of calpastatin. Finally, we, present a model for the calpastatin-inhibited calpain.
+The Ca(2+)-dependent cysteine protease calpain along with its endogenous inhibitor calpastatin is widely distributed. The interactions between calpain and calpastatin have been studied to better understand the nature of calpain inhibition by calpastatin, which can aid the design of small molecule inhibitors to calpain. Here we present the crystal structure of a complex between a calpastatin peptide and the calcium-binding domain VI of calpain. DIC19 is a 19 residue peptide, which corresponds to one of the three interacting domains of calpastatin, which is known to interact with domain VI of calpain. We present two crystal structures of DIC19 bound to domain VI of calpain, determined by molecular replacement methods to 2.5A and 2.2A resolution. In the process of crystallizing the inhibitor complex, a new native crystal form was identified which had the homodimer 2-fold axis along a crystallographic axis as opposed to the previously observed dimer in the asymmetric unit. The crystal structures of the native domain VI and its inhibitor PD150606 (3-(4-iodophenyl)-2-mercapto-(Z)-2-propenoic acid) complex were determined with the help of molecular replacement methods to 2.0A and 2.3A resolution, respectively. In addition, we built a homology model for the complex between domain IV and DIA19 peptide of calpastatin. Finally, we present a model for the calpastatin-inhibited calpain.
 ==About this Structure==
-NX0 is a [http://en.wikipedia.org/wiki/Protein_complex Protein complex] structure of sequences from [http://en.wikipedia.org/wiki/Sus_scrofa Sus scrofa] with CA as [http://en.wikipedia.org/wiki/ligand ligand]. Active as [http://en.wikipedia.org/wiki/Hydrolase Hydrolase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.4.22.52 and 3.4.22.53 3.4.22.52 and 3.4.22.53] Full crystallographic information is available from [http://ispc.weizmann.ac.il/oca-bin/ocashort?id=1NX0 OCA].
+NX0 is a [http://en.wikipedia.org/wiki/Protein_complex Protein complex] structure of sequences from [http://en.wikipedia.org/wiki/Sus_scrofa Sus scrofa] with <scene name='pdbligand=CA:'>CA</scene> as [http://en.wikipedia.org/wiki/ligand ligand]. Active as [http://en.wikipedia.org/wiki/Hydrolase Hydrolase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.4.22.52 and 3.4.22.53 3.4.22.52 and 3.4.22.53] Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1NX0 OCA].
 ==Reference==
@@ Line 15: / Line 15: @@
 [[Category: Sus scrofa]]
 [[Category: Chattopadhyay, D.]]
-[[Category: Deivanayagam, C.C.S.]]
+[[Category: Deivanayagam, C C.S.]]
-[[Category: Lin, G.D.]]
+[[Category: Lin, G D.]]
 [[Category: Maki, M.]]
 [[Category: Moore, D.]]
-[[Category: Narayana, S.V.L.]]
+[[Category: Narayana, S V.L.]]
 [[Category: Todd, B.]]
-[[Category: Wang, K.K.W.]]
+[[Category: Wang, K K.W.]]
 [[Category: CA]]
 [[Category: calcium binding]]
 [[Category: hydrolase]]
-''Page seeded by [http://ispc.weizmann.ac.il/oca OCA ] on Tue Nov 20 22:37:57 2007''
+''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 14:11:01 2008''