The enzymological basis for resistance of herpesvirus DNA polymerase mutants to acyclovir: relationship to the structure of alpha-like DNA polymerases.
'Acyclovir (ACV), like many antiviral drugs, is a nucleoside analog. In vitro, ACV triphosphate inhibits herpesvirus DNA polymerase by means of binding, incorporation into primer/template, and dead-end complex formation in the presence of the next deoxynucleoside triphosphate. However, it is not known whether this mechanism operates in vivo. To address ... More
15-Lipoxygenase metabolism of 2-arachidonylglycerol. Generation of a peroxisome proliferator-activated receptor alpha agonist.
Authors Kozak Kevin R; Gupta Rajnish A; Moody John S; Ji Chuan; Boeglin William E; DuBois Raymond N; Brash Alan R; Marnett Lawrence J;
JournalJ Biol Chem
PubMed ID11956198
'The recent demonstrations that cyclooxygenase-2 and leukocyte-type 12-lipoxygenase (LOX) efficiently oxygenate 2-arachidonylglycerol (2-AG) prompted an investigation into related oxygenases capable of metabolizing this endogenous cannabinoid receptor ligand. We evaluated the ability of six LOXs to catalyze the hydroperoxidation of 2-AG. Soybean 15-LOX, rabbit reticulocyte 15-LOX, human 15-LOX-1, and human 15-LOX-2 ... More
Structure of the reovirus membrane-penetration protein, Mu1, in a complex with is protector protein, Sigma3.
Authors Liemann Susanne; Chandran Kartik; Baker Timothy S; Nibert Max L; Harrison Stephen C;
JournalCell
PubMed ID11832217
Cell entry by nonenveloped animal viruses requires membrane penetration without membrane fusion. The reovirus penetration agent is the outer-capsid protein, Mu1. The structure of Mu1, complexed with its ... More
Discovery of a small molecule insulin mimetic with antidiabetic activity in mice [see comments]
AuthorsZhang B, Salituro G, Szalkowski D, Li Z, Zhang Y, Royo I, Vilella D, Diez MT, Pelaez F, Ruby C, Kendall RL, Mao X, Griffin P, Calaycay J, Zierath JR, Heck JV, Smith RG, Moller DE
JournalScience
PubMed ID10320380
Insulin elicits a spectrum of biological responses by binding to its cell surface receptor. In a screen for small molecules that activate the human insulin receptor tyrosine kinase, a nonpeptidyl fungal metabolite (L-783,281) was identified that acted as an insulin mimetic in several biochemical and cellular assays. The compound was ... More
Proteolytic activity of human osteoclast cathepsin K. Expression, purification, activation, and substrate identification.
AuthorsBossard MJ, Tomaszek TA, Thompson SK, Amegadzie BY, Hanning CR, Jones C, Kurdyla JT, McNulty DE, Drake FH, Gowen M, Levy MA
JournalJ Biol Chem
PubMed ID8647860
Human cathepsin K is a recently identified protein with high primary sequence homology to members of the papain cysteine protease superfamily including cathepsins S, L, and B and is selectively expressed in osteoclasts (Drake, F.H., Dodds, R., James I., Connor J., Debouck, C., Richardson, S., Lee, E., Rieman, D., Barthlow, ... More
Regulation of Vav-SLP-76 binding by ZAP-70 and its relevance to TCR zeta/CD3 induction of interleukin-2.
AuthorsRaab M, da Silva AJ, Findell PR, Rudd CE
JournalImmunity
PubMed ID9047237
T cell activation stimulates p56(lck), p59(fyn), ZAP-70, Vav-SLP-76 binding, and IL-2 transcription. Major questions concern the tyrosine- kinase and relevant site(s) needed for Vav-SLP-76 complex formation and its role in IL-2 production. Here, we show that of the three kinases, only ZAP-70 phosphorylates SLP-76 at specific sites that allow Vav ... More
Functional role of p35srj, a novel p300/CBP binding protein, during transactivation by HIF-1.
AuthorsBhattacharya S, Michels CL, Leung MK, Arany ZP, Kung AL, Livingston DM
JournalGenes Dev
PubMed ID9887100
Recruitment of p300/CBP by the hypoxia-inducible factor, HIF-1, is essential for the transcriptional response to hypoxia and requires an interaction between the p300/CBP CH1 region and HIF-1alpha. A new p300- CH1 interacting protein, p35srj, has been identified and cloned. p35srj is an alternatively spliced isoform of MRG1, a human protein ... More
A serine/threonine-rich motif is one of three nuclear localization signals that determine unidirectional transport of the mineralocorticoid receptor to the nucleus.
AuthorsWalther RF, Atlas E, Carrigan A, Rouleau Y, Edgecombe A, Visentin L, Lamprecht C, Addicks GC, Haché RJ, Lefebvre YA,
JournalJ Biol Chem
PubMed ID15737989
The mineralocorticoid receptor (MR) is a tightly regulated nuclear hormone receptor that selectively transmits corticosteroid signals. Steroid treatment transforms MR from a transcriptionally inert state, in which it is distributed equally between the nucleus and cytoplasm, to an active completely nuclear transcription factor. We report here that MR is an ... More
Molecular characterization of major cat allergen Fel d 1: expression of heterodimer by use of a baculovirus expression system.
Fel d 1 is a major cat allergen inducing allergic rhinitis and asthma in sensitized individuals. It has a more complex structure when compared with other allergens and therefore expression of recombinant Fel d 1 has been considered a challenge. The present study shows for the first time that a ... More