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Full-Text Articles in Chemicals and Drugs
Cloning And Characterization Of The Escherichia Coli Heptosyltransferase Iii: Exploring Substrate Specificity In Lipopolysaccaride Core Biosynthesis, Jagadesh Mudapaka, Erika Taylor
Cloning And Characterization Of The Escherichia Coli Heptosyltransferase Iii: Exploring Substrate Specificity In Lipopolysaccaride Core Biosynthesis, Jagadesh Mudapaka, Erika Taylor
Erika A. Taylor, Ph.D.
Bacterial lipopolysaccharide (LPS) molecules are an important cell surface component that enables adhesion to surfaces and cell motility, amongst other functions. In Escherichia coli, there are multiple Heptosyltransferase enzymes involved in the biosynthesis of the core region of LPS. Here we describe the first ever cloning, expression, purification and characterization of Heptosyltransferase III (HepIII) from E. coli, which catalyzes the addition of an l-glycero-d-manno-heptose (Hep) residue to the growing LPS core via an α(1→7) bond. Inspired by results from our lab on the E. coli HepI, we assessed the catalytic efficiency with phospho-Hep2-Kdo2-Lipid A (PH2K2LA) and two deacylated analogues.
Lipopolysaccharide Biosynthesis Without The Lipids: Substrate Recognition For Escherichia Coli Heptosyltransferasei, Daniel J. Czyzyk, Cassie Liu, Erika A. Taylor
Lipopolysaccharide Biosynthesis Without The Lipids: Substrate Recognition For Escherichia Coli Heptosyltransferasei, Daniel J. Czyzyk, Cassie Liu, Erika A. Taylor
Erika A. Taylor, Ph.D.
Heptosyltransferase I (HepI) is responsible for the transfer of l-glycero-d-manno-heptose to a 3-deoxy-α-D-oct-2-ulopyranosonic acid (Kdo) of the growing core region of lipopolysaccharide (LPS). The catalytic efficiency of HepI with the fully deacylated analogue of Escherichia coli HepI LipidA is 12-fold greater than with the fully acylated substrate, with a k(cat)/K(m) of 2.7 × 10(6) M(-1) s(-1), compared to a value of 2.2 × 10(5) M(-1) s(-1) for the Kdo(2)-LipidA substrate. Not only is this is the first demonstration that an LPS biosynthetic enzyme is catalytically enhanced by the absence of lipids, this result has significant implications for downstream enzymes that …
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.