A5107142553- HIV Research and Treatment
- HIV/AIDS drug development and treatment
- Protein Structure and Dynamics
- Monoclonal and Polyclonal Antibodies Research
- Biochemical and Molecular Research
- Enzyme Structure and Function
- Platelet Disorders and Treatments
- Glycosylation and Glycoproteins Research
- Fungal and yeast genetics research
- Bacteriophages and microbial interactions
- Biochemical and Structural Characterization
- Parkinson's Disease Mechanisms and Treatments
- Peptidase Inhibition and Analysis
- Blood Coagulation and Thrombosis Mechanisms
- Chemical Synthesis and Analysis
- Plant Gene Expression Analysis
- Enzyme Production and Characterization
- Cell Adhesion Molecules Research
- Protease and Inhibitor Mechanisms
- Fermentation and Sensory Analysis
- Computational Drug Discovery Methods
- Protein Kinase Regulation and GTPase Signaling
- Spectroscopy and Quantum Chemical Studies
- Nonlinear Optical Materials Research
- Signaling Pathways in Disease
KU Leuven
2010-2019
Kemin (Belgium)
2019
Molecular Research Institute
2012
Research Institute for Chromatography
2007
University of Nottingham
2006
Vlaams Instituut voor Biotechnologie
1997-2003
Transgene (France)
1997
D2S International (Belgium)
1992-1995
VIB-UGent Center for Plant Systems Biology
1989
Antiapoptotic B-cell lymphoma 2 (Bcl-2) targets the inositol 1,4,5-trisphosphate receptor (IP3R) via its BH4 domain, thereby suppressing IP3R Ca2+-flux properties and protecting against Ca2+-dependent apoptosis. Here, we directly compared inhibition by BH4-Bcl-2 BH4-Bcl-Xl. In contrast to BH4-Bcl-2, BH4-Bcl-Xl neither bound modulatory domain of nor inhibited IP3-induced Ca2+ release (IICR) in permeabilized intact cells. We identified a critical residue (Lys17) not conserved (Asp11). Changing...
Nanopores have recently emerged as powerful tools in single-molecule investigations. Biological nanopores, however, drawbacks, including a fixed size and limited stability lipid bilayers. Inspired by the great success of directed evolution approaches tailoring enzyme properties, this work we evolved Cytolysin A from Salmonella typhi (ClyA) to high level soluble expression desired electrical properties Evolved ClyA nanopores remained open up −150 mV applied potential, which allowed detailed...
E527K hyperactive SRC results in megakaryocytes with increased podosome formation, thrombocytopenia, myelofibrosis, bleeding, and bone pathologies.
ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTProtein engineering of xylose (glucose) isomerase from Actinoplanes missouriensis. 1. Crystallography and site-directed mutagenesis metal binding sitesJohn Jenkins, Joel Janin, Felix Rey, Mohammed Chiadmi, Herman Van Tilbeurgh, Ignace Lasters, Marc De Maeyer, Daniel Ven Belle, Shoshana J. Wodak, Cite this: Biochemistry 1992, 31, 24, 5449–5458Publication Date (Print):June 1, 1992Publication History Published online1 May 2002Published inissue 1 June...
Retroviruses by definition insert their viral genome into the host cell chromosome. Although key player of retroviral integration is integrase, a role for cellular cofactors has been proposed. Lentiviral integrases use protein LEDGF/p75 to tether preintegration complex chromosome, although existence alternative proteins substituting function in Truncation mutants lacking chromosome attachment site strongly inhibit HIV replication competition interaction with integrase. In an attempt select...
Mutations in the leucine-rich repeat kinase 2 (LRRK2) gene are most prevalent known cause of autosomal dominant Parkinson's disease. The LRRK2 encodes a Roco protein featuring Ras complex proteins (ROC) GTPase and domain linked by C-terminal ROC (COR) domain. Here, we explored effects Y1699C pathogenic mutation COR on activity interactions within catalytic core LRRK2. We observed decrease for comparable to R1441C mutant T1348N dysfunctional mutant. To study underlying mechanism, dimerization...
Leucine rich repeat kinase 2 (LRRK2) is a Parkinson's disease (PD) gene that encodes large multidomain protein including both GTPase and domain. GTPases often regulate kinases within signal transduction cascades, where act as molecular switches cycling between GTP bound "on" state GDP "off" state. It has been proposed LRRK2 activity may be increased upon binding at the Ras of complex proteins (ROC) Here we extensively test this hypothesis by measuring phosphorylation under influence GDP, or...
Leucine-rich repeat kinase 1 and 2 (LRRK1 LRRK2) are large multidomain proteins containing kinase, GTPase multiple protein-protein interaction domains, but only mutations in LRRK2 linked to familial Parkinson's disease (PD). Independent studies suggest that exists the cell as a complex compatible with size of dimer. However, whether this is truly homodimer or heterologous formed by monomeric other has not been definitively proven due limitations obtaining highly pure suitable for structural...
Although the conformational states of protein side chains can be described using a library rotamers, determination global minimum energy conformation (GMEC) large collection chains, given fixed backbone coordinates, represents challenging combinatorial problem with important applications in field homology modelling. Recently, we have developed theoretical framework, called dead-end elimination method, which allows us to identify efficiently rotamers that cannot members GMEC. Such dead-ending...
ABSTRACT The diketo acid L-708,906 has been reported to be a selective inhibitor of the strand transfer step human immunodeficiency virus type 1 (HIV-1) integration process (D. Hazuda, P. Felock, M. Witmer, A. Wolfe, K. Stillmock, J. Grobler, Espeseth, L. Gabryelski, W. Schleif, C. Blau, and D. Miller, Science 287:646-650, 2000). We have now studied development antiviral resistance by growing HIV-1 strains in presence increasing concentrations compound. mutations T66I, L74M, S230R emerged...
Sarco(endo)plasmic reticulum Ca 2+ ATPase (SERCA) transporters pump cytosolic into the endoplasmic reticulum, maintaining a gradient that controls vital cell functions ranging from proliferation to death. To meet physiological demand of cell, SERCA activity is regulated by adjusting affinity for ions. Of all isoforms, housekeeping SERCA2b isoform displays highest because unique C-terminal extension (2b-tail). Here, an extensive structure–function analysis mutants and SERCA1a2b chimera...
Abstract Cell wall invertases (cwINVs), with a high affinity for the cell wall, are fundamental enzymes in control of plant growth, development, and carbon partitioning. Most interestingly, defective cwINVs have been described several species. Their highly attenuated sucrose (Suc)-hydrolyzing capacity is due to absence aspartate-239 (Asp-239) tryptophan-47 (Trp-47) homologs, crucial players stable binding active site subsequent hydrolysis. However, so far, precise roles such remain unclear....
Leucine-rich repeat kinase 2 (LRRK2) is a complex, multidomain protein which considered valuable target for potential disease-modifying therapeutic strategies Parkinson's disease (PD). In mammalian cells and brain, LRRK2 phosphorylated treatment of with inhibitors activity can induce dephosphorylation at cluster serines including Ser910/935/955/973. It has been suggested that phosphorylation levels these sites reflect activity, however kinase-dead variants or activating do not display...
In all domains of life, the catalysed degradation RNA facilitates rapid adaptation to changing environmental conditions, while destruction foreign is an important mechanism prevent host infection. We have identified a virus-encoded protein termed gp37/Dip, which directly binds and inhibits machinery its bacterial host. Encoded by giant phage фKZ, this associates with two binding sites RNase E component Pseudomonas aeruginosa degradosome, occluding them from substrates resulting in effective...
DNA binding as well ligand by nuclear receptors has been studied extensively. Both functions are attributed to isolated domains of which the structure is known. The crystal a complete receptor in complex with its and DNA-response element, however, solved only for peroxisome proliferator-activated γ (PPARγ)-retinoid X α (RXRα) heterodimer. This provided first indication direct interactions between DNA-binding domain (DBD) ligand-binding (LBD). In this study, we investigated whether there...