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Emergence Of Compensatory Mutations Reveals The Importance Of Electrostatic Interactions Between Hiv-1 Integrase And Genomic Rna, Christian Shema Mugisha, Tung Dinh, Abhishek Kumar, Kasyap Tenneti, Jenna E Eschbach, Keanu Davis, Robert Gifford, Mamuka Kvaratskhelia, Sebla B Kutluay Oct 2022

Emergence Of Compensatory Mutations Reveals The Importance Of Electrostatic Interactions Between Hiv-1 Integrase And Genomic Rna, Christian Shema Mugisha, Tung Dinh, Abhishek Kumar, Kasyap Tenneti, Jenna E Eschbach, Keanu Davis, Robert Gifford, Mamuka Kvaratskhelia, Sebla B Kutluay

2020-Current year OA Pubs

HIV-1 integrase (IN) has a noncatalytic function in virion maturation through its binding to the viral RNA genome (gRNA). Class II IN substitutions inhibit IN-gRNA binding and result in the formation of virions with aberrant morphologies marked by mislocalization of the gRNA between the capsid lattice and the lipid envelope. These viruses are noninfectious due to a block at an early reverse transcription stage in target cells. HIV-1 IN utilizes basic residues within its C-terminal domain (CTD) to bind to the gRNA; however, the molecular nature of how these residues mediate gRNA binding and whether other regions of IN are …


A Dpagt1 Missense Variant Causes Degenerative Retinopathy Without Myasthenic Syndrome In Mice, Lillian F Hyde, Yang Kong, Lihong Zhao, Sriganesh Ramachandra Rao, Jieping Wang, Lisa Stone, Andrew Njaa, Gayle B. Collin, Mark P. Krebs, Bo Chang, Steven J Fliesler, Patsy M. Nishina, Juergen K. Naggert Oct 2022

A Dpagt1 Missense Variant Causes Degenerative Retinopathy Without Myasthenic Syndrome In Mice, Lillian F Hyde, Yang Kong, Lihong Zhao, Sriganesh Ramachandra Rao, Jieping Wang, Lisa Stone, Andrew Njaa, Gayle B. Collin, Mark P. Krebs, Bo Chang, Steven J Fliesler, Patsy M. Nishina, Juergen K. Naggert

Faculty Research 2022

Congenital disorders of glycosylation (CDG) are a heterogenous group of primarily autosomal recessive mendelian diseases caused by disruptions in the synthesis of lipid-linked oligosaccharides and their transfer to proteins. CDGs usually affect multiple organ systems and vary in presentation, even within families. There is currently no cure, and treatment is aimed at ameliorating symptoms and improving quality of life. Here, we describe a chemically induced mouse mutant,


D121 Located Within The Dry Motif Of P2y12 Is Essential For P2y12-Mediated Platelet Function., Carol Dangelmaier, Benjamin Mauri, Akruti Patel, Satya P Kunapuli, John C Kostyak Sep 2022

D121 Located Within The Dry Motif Of P2y12 Is Essential For P2y12-Mediated Platelet Function., Carol Dangelmaier, Benjamin Mauri, Akruti Patel, Satya P Kunapuli, John C Kostyak

Department of Medicine Faculty Papers

Platelets are anucleate cells that mediate hemostasis. This occurs via a primary signal that is reinforced by secreted products such as ADP that bind purinergic receptors (P2Y1 and P2Y12) on the platelet surface. We recently identified a human subject, whom we termed platelet defect subject 25 (PDS25) with a platelet functional disorder associated with the P2Y12 receptor. PDS25 has normal blood cell counts and no history of bleeding diathesis. However, platelets from PDS25 have virtually no response to 2-MeSADP (a stable analogue of ADP). Genetic analysis of P2Y12 from PDS25 revealed a heterozygous mutation of D121N within the DRY motif. …


Synthesis Of A Novel Ras Farnesyl Protein Transferase Inhibitor, Mark F. Mechelke, Anna Mikolchak May 2022

Synthesis Of A Novel Ras Farnesyl Protein Transferase Inhibitor, Mark F. Mechelke, Anna Mikolchak

Chemistry Faculty Publications

Mutant RAS proteins are associated with 30% of all human cancers. Unregulated cell growth caused by mutant RAS proteins can be prevented by RAS farnesyl protein transferase (FPTase) inhibitors. A novel FPTase inhibitor has been synthesized incorporating a modified farnesyl “tail” and a customized diphosphate “head”. It is anticipated that the modified “tail”, incorporating a phenyl substituent, will bind more tightly to FPTase due to nonbonding interactions between the aromatic ring and ten aromatic amino acid residues that line the enzyme active site. The altered polar “head”, designed from L-aspartic acid, has already been shown to mimic the natural substrate’s …