2id4
From Proteopedia
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'''The 1.9 A structure of Kex2 in complex with an Ac-R-E-R-K-chloromethyl ketone inhibitor.''' | '''The 1.9 A structure of Kex2 in complex with an Ac-R-E-R-K-chloromethyl ketone inhibitor.''' | ||
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[[Category: Holyoak, T.]] | [[Category: Holyoak, T.]] | ||
[[Category: Wheatley, J L.]] | [[Category: Wheatley, J L.]] | ||
| - | [[Category: | + | [[Category: Convertase]] |
| - | [[Category: | + | [[Category: Furin]] |
| - | [[Category: | + | [[Category: Kex2]] |
| - | [[Category: | + | [[Category: Kexin]] |
| - | [[Category: | + | [[Category: Prohormone]] |
| - | [[Category: | + | [[Category: Proprotein]] |
| - | [[Category: | + | [[Category: Serine protease]] |
| - | [[Category: | + | [[Category: Subtilisin like protease]] |
| - | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sun May 4 07:21:23 2008'' | |
| - | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on | + | |
Revision as of 04:21, 4 May 2008
The 1.9 A structure of Kex2 in complex with an Ac-R-E-R-K-chloromethyl ketone inhibitor.
Overview
The high-resolution crystal structure of kexin (Kex2) in complex with a peptidyl-chloromethylketone inhibitor containing a noncognate lysine at the P(1) position provides the structural basis for the differential lysine/arginine selectivity that defines the prohormone (proprotein) convertase (PC) family. By comparison with the previous structures of Kex2 and furin, this structure of the acylated enzyme provides a basis for the observed decrease in the acylation rate with substrates containing a lysine at P(1) and the absence of an effect on the deacylation rate without involving mobility of the S(1) lid. The structure of the complex shows that a secondary subsite in the S(1) pocket is present, and that this site recognizes and binds the P(1) lysine in a more shallow fashion than arginine. This results in a displacement of the bound peptide away from the S385 nucleophile relative to substrates containing a P(1) arginine. It is concluded that this alternate binding site and resultant displacement of the scissile bond in the active site results in the observed decrease in the acylation rate. Studies of the inactivation kinetics of Kex2 by two peptidyl chloromethylketone inhibitors demonstrates that the selectivity between lysine and arginine at the P(1) position arises at the acylation step, consistent with what was observed with peptidyl substrates [Rockwell NC, Fuller RS (2001) J Biol Chem 276:38394-38399].
About this Structure
2ID4 is a Single protein structure of sequence from Saccharomyces cerevisiae. Full crystallographic information is available from OCA.
Reference
Differential P1 arginine and lysine recognition in the prototypical proprotein convertase Kex2., Wheatley JL, Holyoak T, Proc Natl Acad Sci U S A. 2007 Apr 17;104(16):6626-31. Epub 2007 Apr 10. PMID:17426142 Page seeded by OCA on Sun May 4 07:21:23 2008
