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Articles 1 - 9 of 9
Full-Text Articles in Chemicals and Drugs
Anopheles Gambiae Purine Nucleoside Phosphorylase: Catalysis, Structure And Inhibition, Erika Taylor, Agnes Rinaldo-Matthis, Lei Li, Mahmoud Ghanem, Keith Hazleton, M. Belen Cassera, Steven Almo, Vern Schramm
Anopheles Gambiae Purine Nucleoside Phosphorylase: Catalysis, Structure And Inhibition, Erika Taylor, Agnes Rinaldo-Matthis, Lei Li, Mahmoud Ghanem, Keith Hazleton, M. Belen Cassera, Steven Almo, Vern Schramm
Erika A. Taylor, Ph.D.
The purine salvage pathway of Anopheles gambiae, a mosquito that transmits malaria, has been identified in genome searches on the basis of sequence homology with characterized enzymes. Purine nucleoside phosphorylase (PNP) is a target for the development of therapeutic agents in humans and purine auxotrophs, including malarial parasites. The PNP from Anopheles gambiae (AgPNP) was expressed in Escherichia coli and compared to the PNPs from Homo sapiens (HsPNP) and Plasmodium falciparum (PfPNP). AgPNP has kcat values of 54 and 41 s-1 for 2'-deoxyinosine and inosine, its preferred substrates, and 1.0 s-1 for guanosine. However, the chemical step is fast for …
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, …
Effects Of Angiotensin 1-7 On The Actions Of Angiotensin Ii In The Renal And Mesenteric Vasculature Of Hypertensive And Streptozotocin-Induced Diabetic Rats, Mohd Rais Mustafa, Murugan Dharmani, Francis I. Achike, Meng-Kwoon Sim
Effects Of Angiotensin 1-7 On The Actions Of Angiotensin Ii In The Renal And Mesenteric Vasculature Of Hypertensive And Streptozotocin-Induced Diabetic Rats, Mohd Rais Mustafa, Murugan Dharmani, Francis I. Achike, Meng-Kwoon Sim
Mohd Rais Mustafa
Angiotensin 1-7, a heptapeptide derived from metabolism of either angiotensin I or angiotensin II, is a biologically active peptide of the renin–angiotensin system. The present study investigated the effect of angiotensin 1-7 on the vasopressor action of angiotensin II in the renal and mesenteric vasculature of Wistar-Kyoto (WKY) rats, spontaneously hypertensive rats (SHR) and streptozotocin-induced diabetic rats. Angiotensin II-induced dose-dependent vasoconstrictions in the renal vasculature. The pressor response was enhanced in the SHR and reduced in the streptozotocin-diabetic rat compared to WKY rats. Angiotensin 1-7 attenuated the angiotensin II pressor responses in the renal vasculature of WKY and SHR rats. …
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.
Ethnic Variations In Paraoxonase1 Polymorphism In The Malaysian Population, Rozaida @ Poh Yuen Ying
Ethnic Variations In Paraoxonase1 Polymorphism In The Malaysian Population, Rozaida @ Poh Yuen Ying
Rozaida @ Poh Yuen Ying
The role of high-density lipoprotein associated paraoxonase (PON) 1 in protection against oxidative stress associated with the development of complications in diabetes mellitus has been reported. Variations in the PON1 gene, 55LM and 192QR have been described in different populations. These variations are known to be risk factors for heart disease, especially the L and R alleles. We have investigated the prevalence of both polymorphisms in the Malaysian population comprising the three major ethnic groups: Malay, Chinese and Indian, using polymerase chain reaction followed by restriction endonuclease digestion. The results show the pooled frequencies of L and R alleles were …
Modulation Of Vascular Reactivity In Normal, Hypertensive And Diabetic Rat Aortae By A Non-Antioxidant Flavonoid, Mohd Rais Mustafa, Macha Ajay, Fracis I. Achike
Modulation Of Vascular Reactivity In Normal, Hypertensive And Diabetic Rat Aortae By A Non-Antioxidant Flavonoid, Mohd Rais Mustafa, Macha Ajay, Fracis I. Achike
Mohd Rais Mustafa
In this study, we report the effects of a non-antioxidant flavonoid flavone on vascular reactivity in Wistar–Kyoto (WKY) rat isolated aortae. Whether flavone directly modulates vascular reactivity in spontaneously hypertensive rat (SHR) and streptozotocin-induced diabetic-WKY rat isolated aortae was also determined. Thoracic aortic rings were mounted in organ chambers and exposed to various drug treatments in the presence of flavone or its vehicle (DMSO), which served as control. Pretreatment with flavone enhanced relaxant effects to endothelium-dependent vasodilator acetylcholine (ACh) and attenuated contractile effects to 1-receptor agonist phenylephrine (PE) in WKY aortae compared to those observed in control aortic rings. Flavone …
Structure And Thermodynamics Of A Conserved U2 Snrna Domain From Yeast And Human, Dipali G. Sashital, Vincenzo Venditti, Courtney G. Angers, Gabriel Cornilescu, Samuel E. Butcher
Structure And Thermodynamics Of A Conserved U2 Snrna Domain From Yeast And Human, Dipali G. Sashital, Vincenzo Venditti, Courtney G. Angers, Gabriel Cornilescu, Samuel E. Butcher
Vincenzo Venditti
The spliceosome is a dynamic ribonucleoprotein complex responsible for the removal of intron sequences from pre-messenger RNA. The highly conserved 5′ end of the U2 small nuclear RNA (snRNA) makes key base-pairing interactions with the intron branch point sequence and U6 snRNA. U2 stem I, a stem–loop located in the 5′ region of U2, has been implicated in spliceosome assembly and may modulate the folding of the U2 and U6 snRNAs in the spliceosome active site. Here we present the NMR structures of U2 stem I from human and Saccharomyces cerevisiae. These sequences represent the two major classes of U2 …