Crystal Structure of the Catalytic Subunit of Cyclic Adenosine Monophosphate-Dependent Protein Kinase

American Association for the Advancement of Science (AAAS) - Tập 253 Số 5018 - Trang 407-414 - 1991
Daniel R. Knighton1, Jianhua Zheng1, Lynn F. Ten Eyck1,2, V. Ashford3, Nguyen‐Huu Xuong3,1,4, Susan S. Taylor1, Janusz M. Sowadski3,5
1Department of Chemistry, University of California, San Diego, La Jolla, CA 92093-0654.
2San Diego Supercomputer Center, San Diego, CA 92186-9784.
3Department of Biology, University of California, San Diego, La Jolla, CA 92093-0317.
4Department of Physics, University of California, San Diego, La Jolla, CA 92093-0319
5Department of Medicine, University of California, San Diego, La Jolla, CA 92093-0654.

Tóm tắt

The crystal structure of the catalytic subunit of cyclic adenosine monophosphate-dependent protein kinase complexed with a 20-amino acid substrate analog inhibitor has been solved and partially refined at 2.7 Å resolution to an R factor of 0.212. The magnesium adenosine triphosphate (MgATP) binding site was located by difference Fourier synthesis. The enzyme structure is bilobal with a deep cleft between the lobes. The cleft is filled by MgATP and a portion of the inhibitor peptide. The smaller lobe, consisting mostly of amino-terminal sequence, is associated with nucleotide binding, and its largely antiparallel β sheet architecture constitutes an unusual nucleotide binding motif. The larger lobe is dominated by helical structure with a single β sheet at the domain interface. This lobe is primarily involved in peptide binding and catalysis. Residues 40 through 280 constitute a conserved catalytic core that is shared by more than 100 protein kinases. Most of the invariant amino acids in this conserved catalytic core are clustered at the sites of nucleotide binding and catalysis.

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American Association for the Advancement of Science (AAAS)

Tập 253 Số 5018

407-414

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