In 2-3 sentences, explain what system the authors are studying in this work. Describe what this system does. 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) -medi- ated 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 inter- faces 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 en- zyme is vital for ATP selectivity. The importance of the hydrogen bond for substrate selectivity is likely general given the conserva- tion of its location and orientation across the family of eukaryotic protein kinases. Please help me. I am quite confusing what the system is.
1A. In 2-3 sentences, explain what system the authors are studying in this work. Describe what this
system does.
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) -medi-
ated 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 inter-
faces 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 en-
zyme is vital for ATP selectivity. The importance of the hydrogen
bond for substrate selectivity is likely general given the conserva-
tion of its location and orientation across the family of eukaryotic
protein kinases.
Please help me. I am quite confusing what the system is.
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