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Articles 1 - 8 of 8
Full-Text Articles in Life Sciences
The Functional Role Of Cysteine Residues For C-Abl Kinase Activity., Amanda Leonberg, Yuh-Cherng Chai
The Functional Role Of Cysteine Residues For C-Abl Kinase Activity., Amanda Leonberg, Yuh-Cherng Chai
Yuh-Cherng Chai
S-glutathionylation, the formation of mixed disulfides of glutathione with cysteine residues of proteins, is a broadly observed physiological modification that occurs in response to oxidative stress. Since cysteine residues are particularly susceptible to oxidative modification by reactive oxygen species, S-glutathionylation can protect proteins from irreversible oxidation. In this study, we show that the kinase activity of the non-receptor tyrosine kinase c-Abl is inhibited by in vitro thiol modification; specifically, the cysteine residues of c-Abl are modified by S-glutathionylation and by thiol alkylating agents such as 4-acetamido-4′-maleimidylstilbene-2,2′-disulfonic acid and N-ethylmaleimide. Modification of cysteine residues of c-Abl tyrosine kinase using glutathione disulfide …
Transition-State Variation In Human, Bovine, And Plasmodium Falciparum Adenosine Deaminases, Minkui Lou, Vipender Singh, Erika Taylor, Vern Schramm
Transition-State Variation In Human, Bovine, And Plasmodium Falciparum Adenosine Deaminases, Minkui Lou, Vipender Singh, Erika Taylor, Vern Schramm
Erika A. Taylor, Ph.D.
Adenosine deaminases (ADAs) from human, bovine, and Plasmodium falciparum sources were analyzed by kinetic isotope effects (KIEs) and shown to have distinct but related transition states. Human adenosine deaminase (HsADA) is present in most mammalian cells and is involved in B- and T-cell development. The ADA from Plasmodium falciparum (PfADA) is essential in this purine auxotroph, and its inhibition is expected to have therapeutic effects for malaria. Therefore, ADA is of continuing interest for inhibitor design. Stable structural mimics of ADA transition states are powerful inhibitors. Here we report the transition-state structures of PfADA, HsADA, and bovine ADA (BtADA) solved …
Acyclic Ribooxacarbenium Ion Mimics As Transition State Analogues Of Human And Malarial Purine Nucleoside Phosphorylases, Erika Taylor, Keith Clinch, Peter Kelly, Lei Li, Gary Evans, Peter Tyler, Vern Schramm
Acyclic Ribooxacarbenium Ion Mimics As Transition State Analogues Of Human And Malarial Purine Nucleoside Phosphorylases, Erika Taylor, Keith Clinch, Peter Kelly, Lei Li, Gary Evans, Peter Tyler, Vern Schramm
Erika A. Taylor, Ph.D.
Transition state analogues of PNP, the Immucillins and DADMe-Immucillins, were designed to match transition state features of bovine and human PNPs, respectively. A third generation of inhibitors has been designed that contain an acyclic iminoalcohol to replace the cyclic mimic of the ribooxacarbenium ion at the transition states of PNPs. The best third generation inhibitor is equivalent to the best inhibitors found in the previous transition state analogues.
Synthesis Of 5‘-Methylthio Coformycins: Specific Inhibitors For Malarial Adenosine Deaminase, Peter Tyler, Erika Taylor, Richard Froehlich, Vern Schramm
Synthesis Of 5‘-Methylthio Coformycins: Specific Inhibitors For Malarial Adenosine Deaminase, Peter Tyler, Erika Taylor, Richard Froehlich, Vern Schramm
Erika A. Taylor, Ph.D.
Transition state theory suggests that enzymatic rate acceleration (kcat/knon) is related to the stabilization of the transition state for a given reaction. Chemically stable analogues of a transition state complex are predicted to convert catalytic energy into binding energy. Because transition state stabilization is a function of catalytic efficiency, differences in substrate specificity can be exploited in the design of tight-binding transition state analogue inhibitors. Coformycin and 2‘-deoxycoformycin are natural product transition state analogue inhibitors of adenosine deaminases (ADAs). These compounds mimic the tetrahedral geometry of the ADA transition state and bind with picomolar dissociation constants to enzymes from bovine, …
Neighboring Group Participation In The Transition State Of Human Purine Nucleoside Phosphorylase, Andrew Murkin, Matthew Birck, Agnes Rinaldo-Matthis, Wuxian Shi, Erika Taylor, Steven Almo, Vern Schramm
Neighboring Group Participation In The Transition State Of Human Purine Nucleoside Phosphorylase, Andrew Murkin, Matthew Birck, Agnes Rinaldo-Matthis, Wuxian Shi, Erika Taylor, Steven Almo, Vern Schramm
Erika A. Taylor, Ph.D.
No abstract provided.
Med19(Rox3) Regulates Intermodule Interactions In The Saccharomyces Cerevisiae Mediator Complex., Shamara Baidoobonso, Benjamin Guidi, Lawrence Myers
Med19(Rox3) Regulates Intermodule Interactions In The Saccharomyces Cerevisiae Mediator Complex., Shamara Baidoobonso, Benjamin Guidi, Lawrence Myers
Shamara M Baidoobonso, PhD
The Saccharomyces cerevisiae Mediator is a 25-subunit complex that facilitates both transcriptional activation and repression. Structural and functional studies have divided Mediator subunits into four distinct modules. The Head, Middle, and Tail modules form the core functional Mediator complex, whereas a fourth, the Cyc-C module, is variably associated with the core. By purifying Mediator from a strain lacking the Med19(Rox3) subunit, we have found that a complex missing only the Med19(Rox3) subunit can be isolated under mild conditions. Additionally, we have established that the entire Middle module is released when the Deltamed19(rox3) Mediator is purified under more stringent conditions. In …
Exercise-Mediated Regulation Of Hsp70 Gene Expression Following Exercise Training, C.W. Melling, David Thorp, Kevin Milne, Matthew Krause, Earl Noble
Exercise-Mediated Regulation Of Hsp70 Gene Expression Following Exercise Training, C.W. Melling, David Thorp, Kevin Milne, Matthew Krause, Earl Noble
Jamie Melling
An issue central to understanding the biological benefits associated with regular exercise training is to elucidate the intracellular mechanisms governing exercise-conferred cardioprotection. Heat shock proteins (HSPs), most notably the inducible 70-kDa HSP family member Hsp70, are believed to participate in the protection of the myocardium during cardiovascular stress. Following acute exercise, activation of PKA mediates the suppression of an intermediary protein kinase, ERK1/2, which phosphorylates and suppresses the activation of the heat shock transcription factor 1 (HSF1). However, following exercise training, ERK1/2 has been reported to regulate the transcriptional activation of several genes involved in cell growth and proliferation and …
Radial Density Distribution And Symmetry Of A Potexvirus, Narcissus Mosaic Virus, Amy Kendall, Wen Bian, Justin Junn, Ian Mccullough, David Gore, Gerald Stubbs
Radial Density Distribution And Symmetry Of A Potexvirus, Narcissus Mosaic Virus, Amy Kendall, Wen Bian, Justin Junn, Ian Mccullough, David Gore, Gerald Stubbs
Ian McCullough
Narcissus mosaic virus is a Potexvirus, a member of the Flexiviridae family of filamentous plant viruses. Fiber diffraction patterns from oriented sols of narcissus mosaic virus have been used to determine the symmetry and structural parameters of the viral helix. The virions have a radius of 55 ± 5 Å. The viral helix has a pitch of 34.45 ± 0.5 Å, with 7.8 subunits per turn of the helix. We conclude that all members of the Potexvirus genus have close to 8 subunits per helical turn.