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Full-Text Articles in Life Sciences

Arginine-178 Is An Essential Residue For Itpa Function, Nicholas E. Burgis, Caitlin April, Kandise Vanwormer Jan 2023

Arginine-178 Is An Essential Residue For Itpa Function, Nicholas E. Burgis, Caitlin April, Kandise Vanwormer

Chemistry and Biochemistry Faculty Publications

The inosine triphosphate pyrophosphatase (ITPA) enzyme plays a critical cellular role by removing noncanonical nucleoside triphosphates from nucleotide pools. One of the first pathological ITPA mutants identified is R178C (rs746930990), which causes a fatal infantile encephalopathy, termed developmental and epileptic encephalopathy 35 (DEE 35). The accumulation of noncanonical nucleotides such as inosine triphosphate (ITP), is suspected to affect RNA and/or interfere with normal nucleotide function, leading to development of DEE 35. Molecular dynamics simulations have shown that the very rare R178C mutation does not significantly perturb the overall structure of the protein, but results in a high level of structural …


Analysis And Exploration Of Novel Antibiotic-Producing Streptomyces Spp. In Spokane County, Washington, Kyle S. Kramer, Jenifer B. Walke Ph.D May 2020

Analysis And Exploration Of Novel Antibiotic-Producing Streptomyces Spp. In Spokane County, Washington, Kyle S. Kramer, Jenifer B. Walke Ph.D

2020 Symposium Posters

According to the Centers for Disease Control and Prevention, a US citizen is infected by an antibiotic-resistant pathogen every 11 seconds, and every 15 minutes, a patient dies as a result of these infections. Due to the increasing incidence of antibiotic-resistant pathogenic microbes, the study and exploration of novel antibiotics from novel environments are imperative as infectious diseases are the second leading cause of death in the United States. The purpose of this research is to investigate and analyze antibiotic-producing soil microbes in Spokane County, WA, with hopes of discovering novel antibiotic-producing microbes, specifically Streptomyces species, and explore some of …


Molecular Docking Study Of Itpa Protein Substrate Complex, Aulane Mpouli May 2020

Molecular Docking Study Of Itpa Protein Substrate Complex, Aulane Mpouli

2020 Symposium Posters

Inosine Triphosphatase (ITPA) is an enzymatic molecule that works to prevent the amassed of an intermediate in the formation of purine nucleotides, Inosine Triphosphate (ITP). DNA consists of purine nucleotides, and its metabolic pathway includes the formation of this intermediate. Overpopulation of ITP causes mutations of DNA leading to cancers, increased Inosine levels in DNA and other immunodeficiencies. In order to regulate the ITP concentration, ITPA binds ITP creating a substrate/enzyme complex. In this study, we used computational docking to explore bound conformation and energy of the binding of ITP to ITPA protein. The docking results reveal how ITPA and …


Structural Dynamics Of Inosine Triphosphate Pyrophosphatase (Itpa) Protein And Two Clinically Relevant Mutants: Molecular Dynamics Simulations, Yao Houndonougbo, Bethany Pugh, Kandise Vanwormer, Caitlin April, Nicholas Burgis Jan 2020

Structural Dynamics Of Inosine Triphosphate Pyrophosphatase (Itpa) Protein And Two Clinically Relevant Mutants: Molecular Dynamics Simulations, Yao Houndonougbo, Bethany Pugh, Kandise Vanwormer, Caitlin April, Nicholas Burgis

Chemistry and Biochemistry Faculty Publications

The inosine triphosphate pyrophosphatase (ITPA) protein is responsible for removing noncanonical purine nucleoside triphosphates from intracellular nucleotide pools. Absence of ITPA results in genomic instability and increased levels of inosine in DNA and RNA. The proline to threonine substitution at position 32 (P32T) affects roughly 15% of the global population and can modulate treatment outcomes for cancer, lupus, and hepatitis C patients. The substitution of arginine with cysteine at position 178 (R178C) is extremely uncommon and has only been reported in a small cohort of early infantile encephalopathy patients suggesting that a functional ITPA protein is required for life in …


A Disease Spectrum For Itpa Variation: Advances In Biochemical And Clinical Research, Nicholas E. Burgis Jan 2016

A Disease Spectrum For Itpa Variation: Advances In Biochemical And Clinical Research, Nicholas E. Burgis

Chemistry and Biochemistry Faculty Publications

Human ITPase (encoded by the ITPA gene) is a protective enzyme which acts to exclude noncanonical (deoxy) nucleoside triphosphates ((d)NTPs) such as (deoxy)inosine 5′-triphosphate ((d)ITP), from (d)NTP pools. Until the last few years, the importance of ITPase in human health and disease has been enigmatic. In 2009, an article was published demonstrating that ITPase deficiency in mice is lethal. All homozygous null offspring died before weaning as a result of cardiomyopathy due to a defect in the maintenance of quality ATP pools. More recently, a whole exome sequencing project revealed that very rare, severe human ITPA mutation results in early …