Kanaujia, Shankar Prasad and Sekar, Kanagaraj (2008) Structures and molecular-dynamics studies of three active-site mutants of bovine pancreatic phospholipase A(2). In: Acta Crystallographica Section D, 64 (Part 1). pp. 1003-1011.
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Phospholipase A(2) hydrolyzes phospholipids at the sn-2 position to cleave the fatty-acid ester bond of L-glycerophospholipids. The catalytic dyad (Asp99 and His48) along with a nucleophilic water molecule is responsible for enzyme hydrolysis. Furthermore, the residue Asp49 in the calcium-binding loop is essential for controlling the binding of the calcium ion and the catalytic action of phospholipase A2. To elucidate the structural role of His48 and Asp49, the crystal structures of three active-site single mutants H48N, D49N and D49K have been determined at 1.9 angstrom resolution. Although the catalytically important calcium ion is present in the H48N mutant, the crystal structure shows that proton transfer is not possible from the catalytic water to the mutated residue. In the case of the Asp49 mutants, no calcium ion was found in the active site. However, the tertiary structures of the three active-site mutants are similar to that of the trigonal recombinant enzyme. Molecular-dynamics simulation studies provide a good explanation for the crystallographic results.
|Item Type:||Journal Article|
|Additional Information:||Copyright of this article belongs to International Union of Crystallography.|
|Department/Centre:||Division of Information Sciences > Supercomputer Education & Research Centre|
|Date Deposited:||04 Jun 2010 08:41|
|Last Modified:||19 Sep 2010 05:58|
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