6F7U

Molecular Mechanism of ATP versus GTP Selectivity of Adenylate Kinase

6F7U の概要

• エントリーDOI: 10.2210/pdb6f7u/pdb
• 分子名称: Adenylate kinase, PHOSPHOMETHYLPHOSPHONIC ACID GUANYLATE ESTER, MAGNESIUM ION, ... (4 entities in total)
• 機能のキーワード: adenylate kinase, atp selectivity, gtp inhibition, inhibitor complex, transferase
• 由来する生物種: Escherichia coli K-12
• 細胞内の位置: Cytoplasm : P69441
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 24165.54

構造登録者

Rogne, P.,Rosselin, M.,Grundstrom, C.,Hedberg, C.,Wolf-Watz, M.,Sauer, U.H. (登録日: 2017-12-12, 公開日: 2018-03-14, 最終更新日: 2024-05-01)

主引用文献

Rogne, P.,Rosselin, M.,Grundstrom, C.,Hedberg, C.,Sauer, U.H.,Wolf-Watz, M.
Molecular mechanism of ATP versus GTP selectivity of adenylate kinase.
Proc. Natl. Acad. Sci. U.S.A., 115:3012-3017, 2018

PubMed Abstract: Enzymatic substrate selectivity is critical for the precise control of metabolic pathways. In cases where chemically related substrates are present inside cells, robust mechanisms of substrate selectivity are required. Here, we report the mechanism utilized for catalytic ATP versus GTP selectivity during adenylate kinase (Adk) -mediated phosphorylation of AMP. Using NMR spectroscopy we found that while Adk adopts a catalytically competent and closed structural state in complex with ATP, the enzyme is arrested in a catalytically inhibited and open state in complex with GTP. X-ray crystallography experiments revealed that the interaction interfaces supporting ATP and GTP recognition, in part, are mediated by coinciding residues. The mechanism provides an atomic view on how the cellular GTP pool is protected from Adk turnover, which is important because GTP has many specialized cellular functions. In further support of this mechanism, a structure-function analysis enabled by synthesis of ATP analogs suggests that a hydrogen bond between the adenine moiety and the backbone of the enzyme is vital for ATP selectivity. The importance of the hydrogen bond for substrate selectivity is likely general given the conservation of its location and orientation across the family of eukaryotic protein kinases.

PubMed: 29507216
DOI: 10.1073/pnas.1721508115

実験手法

X-RAY DIFFRACTION (1.4 Å)