1kn6: Difference between revisions

Revision as of 14:35, 21 February 2008

Solution Structure of the Mouse Prohormone Convertase 1 Pro-Domain

OverviewOverview

The solution structure of the mouse pro-hormone convertase (PC) 1 pro-domain was determined using heteronuclear NMR spectroscopy and is the first structure to be obtained for any of the domains in the convertase family. The ensemble of NMR-derived structures shows a well-ordered core consisting of a four-stranded antiparallel beta-sheet with two alpha-helices packed against one side of this sheet. Sequence homology suggests that the other eukaryotic PC pro-domains will have the same overall fold and most of the residues forming the hydrophobic core of PC1 are highly conserved within the PC family. However, some of the core residues are predicted by homology to be replaced by polar amino acid residues in other PC pro-domains and this may help to explain their marginal stability. Interestingly, the folding topology observed here is also seen for the pro-domain of bacterial subtilisin despite little or no sequence homology. Both the prokaryotic and eukaryotic structures have hydrophobic residues clustered on the solvent-accessible surface of their beta-sheets although the individual residue types differ. In the bacterial case this region is buried at the binding interface with the catalytic domain and, in the eukaryotic PC family, these surface residues are conserved. We therefore propose that the hydrophobic patch in the PC1 pro-domain is involved in the binding interface with its cognate catalytic domain in a similar manner to that seen for the bacterial system. The PC1 pro-domain structure also reveals potential mechanisms for the acid-induced dissociation of the complex between pro- and catalytic domains.

About this StructureAbout this Structure

1KN6 is a Single protein structure of sequence from Mus musculus. Active as Proprotein convertase 1, with EC number 3.4.21.93 Full crystallographic information is available from OCA.

ReferenceReference

Solution structure of the pro-hormone convertase 1 pro-domain from Mus musculus., Tangrea MA, Bryan PN, Sari N, Orban J, J Mol Biol. 2002 Jul 19;320(4):801-12. PMID:12095256

Page seeded by OCA on Thu Feb 21 13:35:53 2008

Proteopedia Page Contributors and Editors (what is this?)Proteopedia Page Contributors and Editors (what is this?)

OCA

@@ Line 1: / Line 1: @@
-[[Image:1kn6.gif|left|200px]]<br /><applet load="1kn6" size="450" color="white" frame="true" align="right" spinBox="true"
+[[Image:1kn6.gif|left|200px]]<br /><applet load="1kn6" size="350" color="white" frame="true" align="right" spinBox="true"
 caption="1kn6" />
 '''Solution Structure of the Mouse Prohormone Convertase 1 Pro-Domain'''<br />
 ==Overview==
-The solution structure of the mouse pro-hormone convertase (PC) 1, pro-domain was determined using heteronuclear NMR spectroscopy and is the, first structure to be obtained for any of the domains in the convertase, family. The ensemble of NMR-derived structures shows a well-ordered core, consisting of a four-stranded antiparallel beta-sheet with two, alpha-helices packed against one side of this sheet. Sequence homology, suggests that the other eukaryotic PC pro-domains will have the same, overall fold and most of the residues forming the hydrophobic core of PC1, are highly conserved within the PC family. However, some of the core, residues are predicted by homology to be replaced by polar amino acid, residues in other PC pro-domains and this may help to explain their, marginal stability. Interestingly, the folding topology observed here is, also seen for the pro-domain of bacterial subtilisin despite little or no, sequence homology. Both the prokaryotic and eukaryotic structures have, hydrophobic residues clustered on the solvent-accessible surface of their, beta-sheets although the individual residue types differ. In the bacterial, case this region is buried at the binding interface with the catalytic, domain and, in the eukaryotic PC family, these surface residues are, conserved. We therefore propose that the hydrophobic patch in the PC1, pro-domain is involved in the binding interface with its cognate catalytic, domain in a similar manner to that seen for the bacterial system. The PC1, pro-domain structure also reveals potential mechanisms for the, acid-induced dissociation of the complex between pro- and catalytic, domains.
+The solution structure of the mouse pro-hormone convertase (PC) 1 pro-domain was determined using heteronuclear NMR spectroscopy and is the first structure to be obtained for any of the domains in the convertase family. The ensemble of NMR-derived structures shows a well-ordered core consisting of a four-stranded antiparallel beta-sheet with two alpha-helices packed against one side of this sheet. Sequence homology suggests that the other eukaryotic PC pro-domains will have the same overall fold and most of the residues forming the hydrophobic core of PC1 are highly conserved within the PC family. However, some of the core residues are predicted by homology to be replaced by polar amino acid residues in other PC pro-domains and this may help to explain their marginal stability. Interestingly, the folding topology observed here is also seen for the pro-domain of bacterial subtilisin despite little or no sequence homology. Both the prokaryotic and eukaryotic structures have hydrophobic residues clustered on the solvent-accessible surface of their beta-sheets although the individual residue types differ. In the bacterial case this region is buried at the binding interface with the catalytic domain and, in the eukaryotic PC family, these surface residues are conserved. We therefore propose that the hydrophobic patch in the PC1 pro-domain is involved in the binding interface with its cognate catalytic domain in a similar manner to that seen for the bacterial system. The PC1 pro-domain structure also reveals potential mechanisms for the acid-induced dissociation of the complex between pro- and catalytic domains.
 ==About this Structure==
-KN6 is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Mus_musculus Mus musculus]. Active as [http://en.wikipedia.org/wiki/Proprotein_convertase_1 Proprotein convertase 1], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.4.21.93 3.4.21.93] Full crystallographic information is available from [http://ispc.weizmann.ac.il/oca-bin/ocashort?id=1KN6 OCA].
+KN6 is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Mus_musculus Mus musculus]. Active as [http://en.wikipedia.org/wiki/Proprotein_convertase_1 Proprotein convertase 1], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.4.21.93 3.4.21.93] Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1KN6 OCA].
 ==Reference==
@@ Line 14: / Line 14: @@
 [[Category: Proprotein convertase 1]]
 [[Category: Single protein]]
-[[Category: Bryan, P.N.]]
+[[Category: Bryan, P N.]]
 [[Category: Orban, J.]]
 [[Category: Sari, N.]]
-[[Category: Tangrea, M.A.]]
+[[Category: Tangrea, M A.]]
 [[Category: beta-alpha-beta-beta-alpha-beta]]
-''Page seeded by [http://ispc.weizmann.ac.il/oca OCA ] on Tue Nov 20 19:23:01 2007''
+''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 13:35:53 2008''