1kfu: Difference between revisions

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[[Image:1kfu.gif|left|200px]]<br />

[[Image:1kfu.gif|left|200px]]<br /><applet load="1kfu" size="350" color="white" frame="true" align="right" spinBox="true"

<applet load="1kfu" size="~~450~~" color="white" frame="true" align="right" spinBox="true"

caption="1kfu, resolution 2.50Å" />

'''Crystal Structure of Human m-Calpain Form II'''<br />

==Overview==

Calpains (calcium-dependent cytoplasmic cysteine proteinases) are, implicated in processes such as cytoskeleton remodeling and signal, transduction. The 2.3-A crystal structure of full-length heterodimeric, [80-kDa (dI-dIV) + 30-kDa (dV+dVI)] human m-calpain crystallized in the, absence of calcium reveals an oval disc-like shape, with the papain-like, catalytic domain dII and the two calmodulin-like domains dIV+dVI occupying, opposite poles, and the tumor necrosis factor alpha-like beta-sandwich, domain dIII and the N-terminal segments dI+dV located between. Compared, with papain, the two subdomains dIIa+dIIb of the catalytic unit are, rotated against one another by 50 degrees, disrupting the active site and, the substrate binding site, explaining the inactivity of calpains in the, absence of calcium. Calcium binding to an extremely negatively charged, loop of domain dIII (an electrostatic switch) could release the adjacent, barrel-like subdomain dIIb to move toward the helical subdomain dIIa, allowing formation of a functional catalytic center. This switch loop, could also mediate membrane binding, thereby explaining calpains' strongly, reduced calcium requirements in vivo. The activity status at the catalytic, center might be further modulated by calcium binding to the calmodulin, domains via the N-terminal linkers.

Calpains (calcium-dependent cytoplasmic cysteine proteinases) are implicated in processes such as cytoskeleton remodeling and signal transduction. The 2.3-A crystal structure of full-length heterodimeric [80-kDa (dI-dIV) + 30-kDa (dV+dVI)] human m-calpain crystallized in the absence of calcium reveals an oval disc-like shape, with the papain-like catalytic domain dII and the two calmodulin-like domains dIV+dVI occupying opposite poles, and the tumor necrosis factor alpha-like beta-sandwich domain dIII and the N-terminal segments dI+dV located between. Compared with papain, the two subdomains dIIa+dIIb of the catalytic unit are rotated against one another by 50 degrees, disrupting the active site and the substrate binding site, explaining the inactivity of calpains in the absence of calcium. Calcium binding to an extremely negatively charged loop of domain dIII (an electrostatic switch) could release the adjacent barrel-like subdomain dIIb to move toward the helical subdomain dIIa, allowing formation of a functional catalytic center. This switch loop could also mediate membrane binding, thereby explaining calpains' strongly reduced calcium requirements in vivo. The activity status at the catalytic center might be further modulated by calcium binding to the calmodulin domains via the N-terminal linkers.

==About this Structure==

1KFU is a [http://en.wikipedia.org/wiki/Protein_complex Protein complex] structure of sequences from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. This structure ~~superseeds~~ the now removed PDB entry 1DKV. 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=1KFU OCA].

1KFU is a [http://en.wikipedia.org/wiki/Protein_complex Protein complex] structure of sequences from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. This structure supersedes the now removed PDB entry 1DKV. 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=1KFU OCA].

==Reference==

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[[Category: thiol-protease]]

''Page seeded by [http://~~ispc~~.weizmann.ac.il/oca OCA ] on ~~Mon Nov 12 17~~:50:~~34 2007~~''

''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 13:33:39 2008''

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@@ Line 1: / Line 1: @@
-[[Image:1kfu.gif|left|200px]]<br />
+[[Image:1kfu.gif|left|200px]]<br /><applet load="1kfu" size="350" color="white" frame="true" align="right" spinBox="true"
-<applet load="1kfu" size="450" color="white" frame="true" align="right" spinBox="true"
 caption="1kfu, resolution 2.50&Aring;" />
 '''Crystal Structure of Human m-Calpain Form II'''<br />
 ==Overview==
-Calpains (calcium-dependent cytoplasmic cysteine proteinases) are, implicated in processes such as cytoskeleton remodeling and signal, transduction. The 2.3-A crystal structure of full-length heterodimeric, [80-kDa (dI-dIV) + 30-kDa (dV+dVI)] human m-calpain crystallized in the, absence of calcium reveals an oval disc-like shape, with the papain-like, catalytic domain dII and the two calmodulin-like domains dIV+dVI occupying, opposite poles, and the tumor necrosis factor alpha-like beta-sandwich, domain dIII and the N-terminal segments dI+dV located between. Compared, with papain, the two subdomains dIIa+dIIb of the catalytic unit are, rotated against one another by 50 degrees, disrupting the active site and, the substrate binding site, explaining the inactivity of calpains in the, absence of calcium. Calcium binding to an extremely negatively charged, loop of domain dIII (an electrostatic switch) could release the adjacent, barrel-like subdomain dIIb to move toward the helical subdomain dIIa, allowing formation of a functional catalytic center. This switch loop, could also mediate membrane binding, thereby explaining calpains' strongly, reduced calcium requirements in vivo. The activity status at the catalytic, center might be further modulated by calcium binding to the calmodulin, domains via the N-terminal linkers.
+Calpains (calcium-dependent cytoplasmic cysteine proteinases) are implicated in processes such as cytoskeleton remodeling and signal transduction. The 2.3-A crystal structure of full-length heterodimeric [80-kDa (dI-dIV) + 30-kDa (dV+dVI)] human m-calpain crystallized in the absence of calcium reveals an oval disc-like shape, with the papain-like catalytic domain dII and the two calmodulin-like domains dIV+dVI occupying opposite poles, and the tumor necrosis factor alpha-like beta-sandwich domain dIII and the N-terminal segments dI+dV located between. Compared with papain, the two subdomains dIIa+dIIb of the catalytic unit are rotated against one another by 50 degrees, disrupting the active site and the substrate binding site, explaining the inactivity of calpains in the absence of calcium. Calcium binding to an extremely negatively charged loop of domain dIII (an electrostatic switch) could release the adjacent barrel-like subdomain dIIb to move toward the helical subdomain dIIa, allowing formation of a functional catalytic center. This switch loop could also mediate membrane binding, thereby explaining calpains' strongly reduced calcium requirements in vivo. The activity status at the catalytic center might be further modulated by calcium binding to the calmodulin domains via the N-terminal linkers.
 ==About this Structure==
-KFU is a [http://en.wikipedia.org/wiki/Protein_complex Protein complex] structure of sequences from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. This structure superseeds the now removed PDB entry 1DKV. 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=1KFU OCA].
+KFU is a [http://en.wikipedia.org/wiki/Protein_complex Protein complex] structure of sequences from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. This structure supersedes the now removed PDB entry 1DKV. 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=1KFU OCA].
 ==Reference==
@@ Line 32: / Line 31: @@
 [[Category: thiol-protease]]
-''Page seeded by [http://ispc.weizmann.ac.il/oca OCA ] on Mon Nov 12 17:50:34 2007''
+''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 13:33:39 2008''