1m4h
|
Crystal Structure of Beta-secretase complexed with Inhibitor OM00-3
OverviewOverview
The structure of the catalytic domain of human memapsin 2 bound to an inhibitor OM00-3 (Glu-Leu-Asp-LeuAla-Val-Glu-Phe, K(i) = 0.3 nM, the asterisk denotes the hydroxyethylene transition-state isostere) has been determined at 2.1 A resolution. Uniquely defined in the structure are the locations of S(3)' and S(4)' subsites, which were not identified in the previous structure of memapsin 2 in complex with the inhibitor OM99-2 (Glu-Val-Asn-LeuAla-Ala-Glu-Phe, K(i) = 1 nM). Different binding modes for the P(2) and P(4) side chains are also observed. These new structural elements are useful for the design of new inhibitors. The structural and kinetic data indicate that the replacement of the P(2)' alanine in OM99-2 with a valine in OM00-3 stabilizes the binding of P(3)' and P(4)'.
About this StructureAbout this Structure
1M4H is a Single protein structure of sequence from Homo sapiens. Full crystallographic information is available from OCA.
ReferenceReference
Crystal structure of memapsin 2 (beta-secretase) in complex with an inhibitor OM00-3., Hong L, Turner RT 3rd, Koelsch G, Shin D, Ghosh AK, Tang J, Biochemistry. 2002 Sep 10;41(36):10963-7. PMID:12206667
Page seeded by OCA on Thu Feb 21 13:51:20 2008