scholarly journals A Novel Function for the N-Terminal Nucleophile Hydrolase Fold Demonstrated by the Structure of an Archaeal Inosine Monophosphate Cyclohydrolase†,‡

Biochemistry ◽  
2007 ◽  
Vol 46 (17) ◽  
pp. 5050-5062 ◽  
Author(s):  
You-Na Kang ◽  
Anh Tran ◽  
Robert H. White ◽  
Steven E. Ealick
Keyword(s):  
Inosine Monophosphate ◽  
Hydrolase Fold ◽  
Inosine Monophosphate Cyclohydrolase

scholarly journals The CRISPR-Cas9 crATIC HeLa transcriptome: Characterization of a novel cellular model of ATIC deficiency and ZMP accumulation

2020 ◽  
Author(s):  
Randall C Mazzarino ◽  
Veronika Baresova ◽  
Marie Zikánová ◽  
Nathan Duval ◽  
Terry G. Wilkinson ◽  
...  
Keyword(s):  
De Novo ◽  
Adenosine Monophosphate ◽  
Acid Synthesis ◽  
Growth Conditions ◽  
Cellular Model ◽  
Inosine Monophosphate ◽  
Cellular Processes ◽  
Exogenous Compounds ◽  
Inosine Monophosphate Cyclohydrolase ◽  
Amp Activated Protein Kinase

ABSTRACTIn de novo purine biosynthesis (DNPS), 5-aminoimidazole-4-carboxamide ribonucleotide formyltransferase (2.1.2.3) / inosine monophosphate cyclohydrolase (3.5.4.10) (ATIC) catalyzes the last two reactions of the pathway: conversion of 5-aminoimidazole-4-carboxamide ribonucleotide [aka Z-nucleotide monophosphate (ZMP)] to 5-formamido-4-imidazolecarboxamide ribonucleotide (FAICAR) then to inosine monophosphate (IMP). ZMP is an adenosine monophosphate (AMP) mimetic and a known activator of AMP-activated protein kinase (AMPK). Recently, a HeLa cell line null mutant for ATIC was constructed via CRISPR-Cas9 mutagenesis. This mutant, crATIC, accumulates ZMP during purine starvation. Given that the mutant can accumulate ZMP in the absence of treatment with exogenous compounds, crATIC is likely an important cellular model of DNPS inactivation and ZMP accumulation. In the current study, we characterize the crATIC transcriptome versus the HeLa transcriptome in purine-supplemented and purine-depleted growth conditions. We report and discuss transcriptome changes with particular relevance to Alzheimer’s disease and in genes relevant to lipid and fatty acid synthesis, neurodevelopment, embryogenesis, cell cycle maintenance and progression, extracellular matrix, immune function, TGFβ and other cellular processes.

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