Rens de Groot
University College London
Binding siteBiophysicsCleavage (embryo)VersicanThrombospondinChemistryImmunologyADAMTSProteaseDisintegrinThrombotic thrombocytopenic purpuraVon Willebrand factorADAMTS13ProteolysisActive siteProtein structureBiochemistryMetalloproteinaseMedicineBiologyScissile bondVon Willebrand factor type A domain
Publications 18
#1Salvatore Santamaria (Imperial College London)H-Index: 14
#2Doretta Cuffaro (UniPi: University of Pisa)H-Index: 5
Last. Josefin Ahnström (Imperial College London)H-Index: 16
view all 10 authors...
ADAMTS-5 is a major protease involved in the turnover of proteoglycans such as aggrecan and versican. Dysregulated aggrecanase activity of ADAMTS-5 has been directly linked to the etiology of osteoarthritis (OA). For this reason, ADAMTS-5 is a pharmaceutical target for the treatment of OA. ADAMTS-5 shares high structural and functional similarities with ADAMTS-4, which makes the design of selective inhibitors particularly challenging. Here we exploited the ADAMTS-5 binding capacity of β-N-acetyl...
4 CitationsSource
#1Salvatore Santamaria (Imperial College London)H-Index: 14
#2Rens de Groot (UCL: University College London)H-Index: 9
Last. Rens de Groot (UCL: University College London)H-Index: 1
view all 2 authors...
The a disintegrin-like and metalloproteinase with thrombospondin motif (ADAMTS) family comprises 19 proteases that regulate the structure and function of extracellular proteins in the extracellular...
5 CitationsSource
#2Rens de GrootH-Index: 9
#1Rens de Groot (Imperial College London)H-Index: 9
: ADAMTS7 is a secreted protease that is predominantly expressed in tissues of the cardiovascular system and tendon. Although recent evidence suggests that it may play a role in the etiology of coronary artery disease, its physiological function and substrates are unknown. The enzyme undergoes extensive posttranslational modifications, including chondroitin sulfate attachment, N and O-linked glycosylation, and a two-step activation process. For the benefit of scientists who study the function of...
2 CitationsSource
#1Anastasis Petri (Imperial College London)H-Index: 2
#2Hyo Jung Kim (University of Nottingham)H-Index: 2
Last. James T. B. Crawley (Imperial College London)H-Index: 30
view all 9 authors...
Platelet recruitment to sites of blood vessel damage is highly dependent upon von Willebrand factor (VWF). VWF platelet-tethering function is proteolytically regulated by the metalloprotease ADAMTS13. Proteolysis depends upon shear-induced conformational changes in VWF that reveal the A2 domain cleavage site. Multiple ADAMTS13 exosite interactions are involved in recognition of the unfolded A2 domain. Here we report through kinetic analyses that, in binding VWF, the ADAMTS13 cysteine-rich and sp...
20 CitationsSource
#1Salvatore Santamaria (Imperial College London)H-Index: 14
#2Kazuhiro Yamamoto (University of Liverpool)H-Index: 17
Last. Josefin Ahnström (Imperial College London)H-Index: 16
view all 8 authors...
ADAMTS (A Disintegrin-like and Metalloproteinase domain with Thrombospondin type 1 Motif)-1, -4 and -5 share the abilities to cleave large aggregating proteoglycans including versican and aggrecan. These activities are highly relevant to cardiovascular disease and osteoarthritis and during development. Here, using purified recombinant ADAMTS-1, -4 and -5, we quantify, compare, and define the molecular basis of their versicanase activity. A novel sandwich-ELISA detecting the major versican cleava...
11 CitationsSource
#1Alain Colige (University of Liège)H-Index: 50
#1Alain Colige (University of Liège)H-Index: 12
Last. Rens de Groot (Imperial College London)H-Index: 9
view all 5 authors...
: The protease ADAMTS7 functions in the extracellular matrix (ECM) of the cardiovascular system. However, its physiological substrate specificity and mechanism of regulation remain to be explored. To address this, we conducted an unbiased substrate analysis using terminal amine isotopic labeling of substrates (TAILS). The analysis identified candidate substrates of ADAMTS7 in the human fibroblast secretome, including proteins with a wide range of functions, such as collagenous and noncollagenous...
12 CitationsSource
#1Salvatore Santamaria (Imperial College London)H-Index: 14
#2Rens de Groot (Imperial College London)H-Index: 9
The metzincin clan of metalloproteinases includes the MMP, ADAM and ADAMTS families, which cleave extracellular targets in a wide range of (patho)physiological processes. Antibodies constitute a powerful tool to modulate the activity of these enzymes for both therapeutic and research purposes. In this review, we give an overview of monoclonal antibodies (mAbs) that have been tested in preclinical disease models, human trials and important studies of metzincin structure and function. Initial atte...
22 CitationsSource
#1Mari Thomas (UCL: University College London)H-Index: 12
#2Rens de Groot (Imperial College London)H-Index: 9
Last. James T. B. Crawley (Imperial College London)H-Index: 30
view all 4 authors...
Abstract Background Acquired thrombotic thrombocytopenic purpura (TTP) is an autoimmune disease in which anti-ADAMTS13 autoantibodies cause severe enzyme deficiency. ADAMTS13 deficiency causes the loss of regulation of von Willebrand factor multimeric size and platelet-tethering function, which results in the formation of disseminated microvascular platelet microthrombi. Precisely how anti-ADAMTS13 autoantibodies, or antibody subsets, cause ADAMTS13 deficiency (ADAMTS13 activity generally Method...
60 CitationsSource
#1Rens de Groot (Imperial College London)H-Index: 9
#2David A. Lane (Imperial College London)H-Index: 11
Last. James T. B. Crawley (Imperial College London)H-Index: 30
view all 3 authors...
ADAMTS13 proteolytically regulates the platelet-tethering function of von Willebrand factor (VWF). ADAMTS13 function is dependent upon multiple exosites that specifically bind the unraveled VWF A2 domain and enable proteolysis. We carried out a comprehensive functional analysis of the ADAMTS13 cysteine-rich (Cys-rich) domain using engineered glycans, sequence swaps, and single point mutations in this domain. Mutagenesis of Cys-rich domain–charged residues had no major effect on ADAMTS13 function...
21 CitationsSource