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PDBsum entry 1m4h
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Hydrolase/hydrolase inhibitor
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PDB id
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1m4h
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Contents |
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* Residue conservation analysis
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References listed in PDB file
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Key reference
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Title
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Crystal structure of memapsin 2 (beta-Secretase) in complex with an inhibitor om00-3.
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Authors
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L.Hong,
R.T.Turner,
G.Koelsch,
D.Shin,
A.K.Ghosh,
J.Tang.
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Ref.
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Biochemistry, 2002,
41,
10963-10967.
[DOI no: ]
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PubMed id
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Abstract
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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)'.
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