A5004935411- Calcium signaling and nucleotide metabolism
- Adenosine and Purinergic Signaling
- PARP inhibition in cancer therapy
- Piperaceae Chemical and Biological Studies
- Sirtuins and Resveratrol in Medicine
- Carbohydrate Chemistry and Synthesis
- Ion Channels and Receptors
- Ion channel regulation and function
- Synthesis and Biological Evaluation
- Toxin Mechanisms and Immunotoxins
- Porphyrin Metabolism and Disorders
- Advanced biosensing and bioanalysis techniques
- Glycosylation and Glycoproteins Research
- Tryptophan and brain disorders
- Biochemical and Molecular Research
- DNA and Nucleic Acid Chemistry
- Electrochemical sensors and biosensors
- Enzyme function and inhibition
- Microbial Metabolism and Applications
- Epigenetics and DNA Methylation
- Drug Transport and Resistance Mechanisms
- PI3K/AKT/mTOR signaling in cancer
- Pharmacogenetics and Drug Metabolism
- Calpain Protease Function and Regulation
- Chemical Synthesis and Characterization
University of Toledo
2015-2024
Temple University
2021
University of Minnesota
2005
Oregon Health & Science University
2004
University of Wisconsin–Madison
2004
Markey Cancer Center
2003
University of Kentucky
1998-2003
University of Arizona
2003
Harvard University
1999
The University of Texas Health Science Center at San Antonio
1988-1991
The Silent information regulator 2 (Sir2) family of enzymes consists NAD+-dependent histone/protein deacetylases that tightly couple the hydrolysis NAD+ and deacetylation an acetylated substrate to form nicotinamide, deacetylated product, novel metabolite O-acetyl-ADP-ribose (OAADPR). In this paper, we analyzed specificity yeast Sir2 (ySir2), HST2, human SIRT2 homologues toward various monoacetylated histone H3 H4 peptides, determined basic kinetic mechanism, resolved individual chemical...
Nicotinic acid adenine dinucleotide phosphate (NAADP) is an agonist-generated second messenger that releases Ca2+ from intracellular acidic stores. Recent evidence has identified the two-pore channels (TPCs) within endolysosomal system as NAADP-regulated release organellar in response to NAADP. However, little known about mechanism coupling NAADP binding calcium release. To identify site, we employed a photoaffinity labeling method using radioactive photoprobe based on 5-azido-NAADP...
Nicotinic acid adenine dinucleotide phosphate (NAADP) is a messenger that regulates calcium release from intracellular acidic stores. Recent studies have identified two-pore channels (TPCs) as endolysosomal are regulated by NAADP; however, the nature of NAADP receptor binding site unknown. To further study sites, we synthesized and characterized [32P-5-azido]nicotinic ([32P-5N3]NAADP) photoaffinity probe. Photolysis sea urchin egg homogenates preincubated with [32P-5N3]NAADP resulted in...
A protein that enables the activation of two-pore channels by NAADP is identified.
The second messenger nicotinic acid adenine dinucleotide phosphate (NAADP) evokes calcium ion (Ca 2+ ) release from endosomes and lysosomes by activating two-pore channels (TPCs) on these organelles. Rather than directly binding to TPCs, NAADP associates with proteins that indirectly confer sensitivity the TPC complex. We investigated whether how NAADP-binding Jupiter microtubule–associated homolog 2 (JPT2) like-Sm protein 12 (LSM12) contributed NAADP-TPC-Ca signaling in human cells....
Nicotinic acid adenine dinucleotide phosphate (NAADP) is a messenger that regulates calcium release from intracellular acidic stores. Although several channels, including two-pore channels (TPC), ryanodine receptor (RYR) and mucolipin (TRP-ML1) have been implicated in NAADP regulation of signaling, the has not identified. In this study, photoaffinity probe, [32P]-5-azido-NAADP ([32P]-5-N3-NAADP), was used to study binding proteins extracts responsive Jurkat T-lymphocytes. [32P]-5-N3-NAADP...
ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTSpecific Inhibition of Poly(ADP-ribose) Glycohydrolase by Adenosine Diphosphate (Hydroxymethyl)pyrrolidinediolJames T. Slama, Nasreen Aboul-Ela, Deepa M. Goli, Bruce V. Cheesman, Anne Simmons, and Myron K. JacobsonCite this: J. Med. Chem. 1995, 38, 2, 389–393Publication Date (Print):January 1, 1995Publication History Published online1 May 2002Published inissue 1 January 1995https://doi.org/10.1021/jm00002a021RIGHTS & PERMISSIONSArticle...
ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTSemisynthetic enzymes: characterization of isomeric flavopapains with widely different catalytic efficienciesJames T. Slama, Czestaw Radziejewski, SubbaRao Oruganti, and E. KaiserCite this: J. Am. Chem. Soc. 1984, 106, 22, 6778–6785Publication Date (Print):October 1, 1984Publication History Published online1 May 2002Published inissue 1 October 1984https://pubs.acs.org/doi/10.1021/ja00334a053https://doi.org/10.1021/ja00334a053research-articleACS...
ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTPorphyrin-protein bond of cytochrome c. Structure porphyrin cJames T. Slama, Herman W. Smith, C. Grant Willson, and Henry RapoportCite this: J. Am. Chem. Soc. 1975, 97, 22, 6556–6562Publication Date (Print):October 1, 1975Publication History Published online1 May 2002Published inissue 1 October 1975https://doi.org/10.1021/ja00855a045Request reuse permissionsArticle Views261Altmetric-Citations33LEARN ABOUT THESE METRICSArticle Views are the...
ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTCarbanicotinamide adenine dinucleotide: synthesis and enzymological properties of a carbocyclic analog oxidized nicotinamide dinucleotideJames T. Slama Anne M. SimmonsCite this: Biochemistry 1988, 27, 1, 183–193Publication Date (Print):January 1988Publication History Published online1 May 2002Published inissue 1 January 1988https://pubs.acs.org/doi/10.1021/bi00401a028https://doi.org/10.1021/bi00401a028research-articleACS PublicationsRequest reuse...
Analogues of nicotinic acid adenine dinucleotide phosphate (NAADP) with substitution at either the 4- or 5-position position moiety have been synthesized from NADP enzymatically using Aplysia californica ADP-ribosyl cyclase mammalian NAD glycohydrolase. Substitution 4-position resulted in loss agonist potency for release Ca2+-ions sea urchin egg homogenates and competition ligand binding assays [32P]NAADP. In contrast, several 5-substituted NAADP derivatives showed high full activity Ca2+...
Polyadenosine diphosphoribose glycohydrolase (PARG) catalyzes the intracellular hydrolysis of adenosine polymers. Because structure−activity data are lacking for PARG, specific inhibitor diphosphate (hydroxymethyl)pyrrolidinediol (ADP-HPD) was utilized to determine effects structure on potency using PARG isolated from bovine thymus (bPARG) and recombinant catalytic fragment (rPARG-CF). Both enzymes were strongly inhibited by submicromolar levels ADP-HPD, but ADP phosphorylated pyrrolidine...
ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTInhibition of NAD glycohydrolase and ADP-ribosyl transferases by carbocyclic analogs oxidized nicotinamide adenine dinucleotideJames T. Slama Anne M. SimmonsCite this: Biochemistry 1989, 28, 19, 7688–7694Publication Date (Print):September 1989Publication History Published online1 May 2002Published inissue 19 September 1989https://pubs.acs.org/doi/10.1021/bi00445a025https://doi.org/10.1021/bi00445a025research-articleACS PublicationsRequest reuse...
ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTSemisynthetic enzymes: synthesis of a new flavopapain with high catalytic efficiencyJames T. Slama, Subba Rao Oruganti, and E. KaiserCite this: J. Am. Chem. Soc. 1981, 103, 20, 6211–6213Publication Date (Print):October 1, 1981Publication History Published online1 May 2002Published inissue 1 October 1981https://pubs.acs.org/doi/10.1021/ja00410a040https://doi.org/10.1021/ja00410a040research-articleACS PublicationsRequest reuse permissionsArticle...
Carba-NAD and pseudocarba-NAD are carbocyclic analogues of NAD+ in which a 2,3-dihydroxycyclopentane methanol replaces the β-d-ribonucleotide ring nicotinamide riboside moiety [Slama Simmons (1988) Biochemistry 27, 183–193]. These analogues, related to each other as diastereomers, have been tested inhibitors intrinsic glycohydrolase activity human CD38, dog spleen glycohydrolase, mouse CD38 Aplysia californicacADP-ribose synthetase. Pseudocarba-NAD, dinucleotide l-2,3-dihydroxycyclopentane...
Polymers of ADP-ribose involved in the maintenance genomic integrity are converted to free by action poly(ADP-ribose) glycohydrolase (PARG). As an approach mapping functions PARG onto amino acid sequence protein, we report here experiments that identify residue binding potent inhibitors. A photoreactive inhibitor, [alpha-(32)P]-8-azidoadenosine diphosphate (hydroxymethyl)pyrrolidinediol (8-N(3)-ADP-HPD), was used photolabel a recombinant bovine catalytic fragment (rPARG-CF). N-Terminal...
Nicotinic acid adenine dinucleotide phosphate (NAADP) is a Ca2+ releasing intracellular second messenger in both mammals and echinoderms. We report that large functionalized substituents introduced at the nicotinic 5-position are recognized by sea urchin receptor, albeit with 20–500-fold loss agonist potency. 5-(3-Azidopropyl)-NAADP was shown to release an EC50 of 31 μM compete NAADP for receptor binding IC50 56 nM. Attachment charged groups associated activity, suggesting nicotinate...