A5008447408- Mitochondrial Function and Pathology
- Receptor Mechanisms and Signaling
- Neuropeptides and Animal Physiology
- Pancreatic function and diabetes
- Enzyme Catalysis and Immobilization
- Genetic Neurodegenerative Diseases
- Parkinson's Disease Mechanisms and Treatments
- Cancer, Hypoxia, and Metabolism
- Heat shock proteins research
- Computational Drug Discovery Methods
- Pharmacology and Obesity Treatment
- Cellular transport and secretion
- Ubiquitin and proteasome pathways
- Natural Antidiabetic Agents Studies
- Lipid Membrane Structure and Behavior
- Chemical Synthesis and Analysis
- Diabetes Management and Research
- Pharmacological Receptor Mechanisms and Effects
- Melanoma and MAPK Pathways
- Drug Transport and Resistance Mechanisms
- Metabolomics and Mass Spectrometry Studies
- Identification and Quantification in Food
- Signaling Pathways in Disease
- Adipose Tissue and Metabolism
- Neurotransmitter Receptor Influence on Behavior
Bioneer (Denmark)
2024
Lundbeck (Denmark)
2009-2020
Granta Design (United Kingdom)
2017
Nordic Bioscience (Denmark)
2009
Novo Nordisk (Denmark)
1993-1997
Architecture et Fonction des Macromolécules Biologiques
1997
Centre National de la Recherche Scientifique
1997
Rigshospitalet
1996-1997
University of Copenhagen
1995-1997
Abstract Genetic variation in the leucine-rich repeat kinase 2 ( LRRK2 ) gene is associated with risk of familial and sporadic Parkinson’s disease (PD). To support clinical development inhibitors as disease-modifying treatment PD biomarkers for activity, target engagement inhibition are prerequisite tools. In a combined proteomics phosphoproteomics study on human peripheral mononuclear blood cells (PBMCs) treated inhibitor Lu AF58786 number putative were identified. Among phospho-site hits...
ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTEvidence for a Pancreatic Lipase Subfamily with New Kinetic PropertiesKenneth Thirstrup, Robert Verger, and Frederic CarriereCite this: Biochemistry 1994, 33, 10, 2748–2756Publication Date (Print):March 15, 1994Publication History Published online1 May 2002Published inissue 15 March 1994https://pubs.acs.org/doi/10.1021/bi00176a002https://doi.org/10.1021/bi00176a002research-articleACS PublicationsRequest reuse permissionsArticle...
Previously metal-ion sites have been used as structural and functional probes in seven transmembrane receptors (7TM), but yet all the engineered inactivating. Based on presumed agonist interaction points III (TM-III) -VII of β 2 -adrenergic receptor, this paper we construct an activating site between amine-binding Asp-113 TM-III—or a His residue introduced at position—and Cys substituted for Asn-312 TM-VII. No increase constitutive activity was observed mutant receptors. Signal transduction...
Very limited structural information is available concerning the superfamily of G-protein-coupled receptors with their seven-transmembrane segments. Recently a non-peptide antagonist site was structurally and functionally replaced by metal ion in tachykinin NK-1 receptor. Here, this Zn(II) transferred to kappa-opioid receptor substituting two residues at outer portion transmembrane V (TM-V), Asp223 Lys227, one residue top TM-VI, Ala298, histidyl residues. The had no direct effect on binding...
Using restriction fragment differential display (RFDD) technology, we have identified the imprinted gene neuronatin (Nnat) as a hypothalamic target under influence of leptin. Nnat mRNA expression is decreased in several key appetite regulatory nuclei rodents with impaired leptin signaling and during fasting conditions. Furthermore, peripheral administration to ob/ob mice normalizes expression. Comparative immunohistochemical analysis human rat hypothalami demonstrates that NNAT protein...
Mutations in leucine-rich repeat kinase 2 (LRRK2), such as G2019S, are associated with an increased risk of developing Parkinson's disease. Surrogates for the LRRK2 domain based on checkpoint 1 (CHK1) mutants were designed, expressed insect cells infected baculovirus, purified, and crystallized. X-ray structures surrogates complexed known inhibitors rationalized compound potency selectivity. The CHK1 10-point mutant was preferred, following assessment surrogate binding affinity inhibitors....
We designed chimeric mutants by exchanging the lid domains of classical human pancreatic lipase (HPL) and guinea pig related protein 2 (GPLRP2). This latter enzyme possesses naturally a large deletion within domain is not activated lipid/water interfaces. Furthermore, GPLRP2 exhibits phospholipase A1 activities in same order magnitude, whereas HPL has no significant activity displays clear interfacial activation. An mutant [HPL(−lid)] with mini-lid does display Its specific toward...
The structural determinants for the selective binding of nonpeptide opioid receptor antagonist nor-binaltorphimine (nor-BNI) to kappa-opioid were characterized using a systematic series chimeras between kappa and homologous mu-opioid receptor. All 10 chimeric constructs bound nonselective antagonists (-)-naloxone diprenorphine with similar affinities, as did two wild-type receptors. Introduction amino-terminal segments increasing length, extending including transmembrane segment VI, from mu...
A cDNA clone encoding the sequence of human pancreatic lipase (HPL) was subcloned into baculovirus transfer vector pVL1392 and used in co‐transfection Spodoptera frugiperda (Sf9) insect cells with wild‐type Autographa californica nuclear polyhedrosis virus (AcNPV) DNA. single recombinant protein (50 kDa) secreted by Sf9 detectable culture medium 24 h post‐infection using both anti‐HPL polyclonal antibodies potentiometric measurements lipolytic activity. The expression level reached 40 mg/l...
GPR139 is an orphan G-protein coupled receptor (GPCR) which primarily expressed in the central nervous system (CNS). In order to explore biological function of this receptor, selective tool compounds are required. A screening campaign identified compound 1a as a high potency agonist with EC50 = 39 nM calcium mobilization assay CHO-K1 cells stably expressing receptor. absence known endogenous ligand, maximum effect was set 100% for 1a. Screening against 90 diverse targets revealed no...
Pediocin PA-1, which is a bacteriocin produced by lactic acid bacteria, has potential as biopreservative of food. However, such use may lead to the development resistance in target organism. Gene expression two independent pediocin-resistant mutants Listeria monocytogenes 412 was compared original isolate restriction fragment differential display PCR (RFDD-PCR). This method amplifies cDNA fragments under stringent conditions, enabled specific primers complementary ligated adaptor sequences....
Starting from total pancreatic mRNAs, the classical guinea pig lipase was cloned using rapid amplification of 3' and 5' cDNA ends. Internal oligonucleotide primers were designed a partial clone including region coding for lid domain. Using this strategy, we did not amplify corresponding to related protein 2 in which domain is deleted. Amino acid sequences compared based on primary tertiary structures human lipase. Their distinct physiological roles are discussed light functional amino differences.
J. Neurochem. (2010) 115 , 209–219. Abstract Hypoxia‐inducible factor (HIF) controls the expression of genes that adapts cellular condition to accommodate oxidative stress. The potential beneficial effect HIF up‐regulation in ischemia has recently gained interest substantiated by known HIF‐regulation erythropoietin and other hypoxia accommodating genes. So far perspectives for been focused on anemia related diseases but little information is available about relevance biology...
Journal Article Structure–function relationships in naturally occurring mutants of pancreatic lipase Get access Frédéric CarriÈre, CarriÈre 1 1To whom correspondence should be addressed Search for other works by this author on: Oxford Academic PubMed Google Scholar Kenneth Thirstrup, Thirstrup Esper Boel, Boel Robert Verger, Verger 2Laboratoire de Lipolyse EnzymatiqueERS 26–CNRS, 31, Chemin Joseph Aiguier, F-13402 Marseille, France Lars Thim Protein Engineering, Design and Selection, Volume...
The transcription factor hypoxia-inducible (HIF) is essential for the activation of several genes that promote survival cells exposed to oxidative stress. Expression tyrosine hydroxylase (TH), which rate-limiting enzyme in dopamine (DA) synthesis, one are positively regulated by HIF. Accordingly, HIF induction results elevated DA release various cell lines vitro. prolyl (HPH) critically involved negative regulation levels. We investigated vivo effects HPH inhibitor FG0041 on brain function...
A series of kappa/mu receptor chimeras and a number kappa receptors substituted in the second transmembrane segment (TM-II) were investigated using as radioligands, respectively, kappa-selective agonist [3H]C1977 nonselective opioid antagonist [3H]diprenorphine (DIP). All constructs bound [3H]DIP with similar high affinity, whereas apparent affinity nonpeptide C1977, when estimated competition binding [3H]DIP, was impaired between 42- > 500-fold 64- 153-fold three mutants that had been TM-II...
The physiological role of pancreatic lipases has traditionally been assigned solely to triacylglyceride metabolism, while the digestion phospholipids requires presence phospholipase A 2 , a 14‐kDa enzyme unrelated lipases. However, in guinea pig, it was observed that absent and pig pancreatic‐lipase‐related protein (GPL‐RP2) responsible for activity, contrast situation other mammalian species. As is member hystricomorph rodents, interest investigate if species within this evolutionary...
Abstract Leucine-rich repeat kinase 2 (LRRK2) is associated to Parkinson’s disease (PD). The most common form of LRRK2 PD caused by the G2019S variant. Besides G2019S, eight other variants causing familial also have amino acid substitutions located in a enzymatic domainsuggesting that activity at core mechanisms underlying risk. Common polymorphic risk variations such as G2385R, A419V, R1628 and M1646T all reside domains. Prior knowledge limited on how these influence function. To...