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Title
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Crystal structure of calcium bound domain VI of calpain at 1.9 A resolution and its role in enzyme assembly, regulation, and inhibitor binding.
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Authors
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G.D.Lin,
D.Chattopadhyay,
M.Maki,
K.K.Wang,
M.Carson,
L.Jin,
P.W.Yuen,
E.Takano,
M.Hatanaka,
L.J.DeLucas,
S.V.Narayana.
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Ref.
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Nat Struct Biol, 1997,
4,
539-547.
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PubMed id
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Abstract
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The three dimensional structure of calcium-bound domain VI of porcine calpain
has been determined to 1.9 A resolution. The crystal structure reveals five
EF-hands, one more than previously suggested. There are two EF-hand pairs, one
pair (EF1-EF2) displays an 'open' conformation and the other (EF3-EF4) a
'closed' conformation. Unusually, a calcium atom is found at the C-terminal end
of the calcium binding loop of EF4. With two additional residues in the calcium
binding loop, the fifth EF-hand (EF5) is in a 'closed' conformation. EF5 pairs
up with the corresponding fifth EF-hand of a non-crystallographically related
molecule. Considering the EF5's role in a homodimer formation of domain VI, we
suggest a model for the assembly of heterodimeric calpain. The crystal structure
of a Ca2+ bound domain VI-inhibitor (PD150606) complex has been refined to 2.1 A
resolution. A possible mode for calpain inhibition is discussed.
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