4OFF

Crystal structure of apo carboxy cGMP binding domain of Plasmodium falciparum PKG

4OFF の概要

• エントリーDOI: 10.2210/pdb4off/pdb
• 関連するPDBエントリー: 4OFG
• 分子名称: CGMP-dependent protein kinase, SULFATE ION (3 entities in total)
• 機能のキーワード: phosphate binding cassette/cyclic gmp binding domain/pkg, serine/threonine kinase, tf2i, irag, cgmp binding, transferase
• 由来する生物種: Plasmodium falciparum
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 17338.68

構造登録者

Kim, J.J.,Sanabria figueroa, E.,Kim, C. (登録日: 2014-01-14, 公開日: 2015-01-21, 最終更新日: 2024-02-28)

主引用文献

Kim, J.J.,Flueck, C.,Franz, E.,Sanabria-Figueroa, E.,Thompson, E.,Lorenz, R.,Bertinetti, D.,Baker, D.A.,Herberg, F.W.,Kim, C.
Crystal Structures of the Carboxyl cGMP Binding Domain of the Plasmodium falciparum cGMP-dependent Protein Kinase Reveal a Novel Capping Triad Crucial for Merozoite Egress.
Plos Pathog., 11:e1004639-e1004639, 2015

PubMed Abstract: The Plasmodium falciparum cGMP-dependent protein kinase (PfPKG) is a key regulator across the malaria parasite life cycle. Little is known about PfPKG's activation mechanism. Here we report that the carboxyl cyclic nucleotide binding domain functions as a "gatekeeper" for activation by providing the highest cGMP affinity and selectivity. To understand the mechanism, we have solved its crystal structures with and without cGMP at 2.0 and 1.9 Å, respectively. These structures revealed a PfPKG-specific capping triad that forms upon cGMP binding, and disrupting the triad reduces kinase activity by 90%. Furthermore, mutating these residues in the parasite prevents blood stage merozoite egress, confirming the essential nature of the triad in the parasite. We propose a mechanism of activation where cGMP binding allosterically triggers the conformational change at the αC-helix, which bridges the regulatory and catalytic domains, causing the capping triad to form and stabilize the active conformation.

PubMed: 25646845
DOI: 10.1371/journal.ppat.1004639

実験手法

X-RAY DIFFRACTION (1.888 Å)