1m4h
From Proteopedia
(New page: 200px<br /> <applet load="1m4h" size="450" color="white" frame="true" align="right" spinBox="true" caption="1m4h, resolution 2.1Å" /> '''Crystal Structure of...) |
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| - | [[Image:1m4h.gif|left|200px]]<br /> | + | [[Image:1m4h.gif|left|200px]]<br /><applet load="1m4h" size="350" color="white" frame="true" align="right" spinBox="true" |
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caption="1m4h, resolution 2.1Å" /> | caption="1m4h, resolution 2.1Å" /> | ||
'''Crystal Structure of Beta-secretase complexed with Inhibitor OM00-3'''<br /> | '''Crystal Structure of Beta-secretase complexed with Inhibitor OM00-3'''<br /> | ||
==Overview== | ==Overview== | ||
| - | The structure of the catalytic domain of human memapsin 2 bound to an | + | 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 Structure== | ==About this Structure== | ||
| - | 1M4H is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http:// | + | 1M4H is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1M4H OCA]. |
==Reference== | ==Reference== | ||
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[[Category: Homo sapiens]] | [[Category: Homo sapiens]] | ||
[[Category: Single protein]] | [[Category: Single protein]] | ||
| - | [[Category: Ghosh, A | + | [[Category: Ghosh, A K.]] |
[[Category: Hong, L.]] | [[Category: Hong, L.]] | ||
[[Category: Koelsch, G.]] | [[Category: Koelsch, G.]] | ||
[[Category: Tang, J.]] | [[Category: Tang, J.]] | ||
| - | [[Category: Turner, R | + | [[Category: Turner, R T.]] |
[[Category: acid protease]] | [[Category: acid protease]] | ||
[[Category: alzheimer's disease]] | [[Category: alzheimer's disease]] | ||
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[[Category: memapsin2]] | [[Category: memapsin2]] | ||
| - | ''Page seeded by [http:// | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 13:51:20 2008'' |
Revision as of 11:51, 21 February 2008
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Crystal Structure of Beta-secretase complexed with Inhibitor OM00-3
Overview
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 Structure
1M4H is a Single protein structure of sequence from Homo sapiens. Full crystallographic information is available from OCA.
Reference
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
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