Jacek Otlewski
University of Wrocław
Binding siteBiophysicsMutantMolecular biologyCytotoxic T cellReceptorEnzymeChemistryPhage displayTrypsin inhibitorChymotrypsinTrypsinProtein structureBiochemistryStereochemistryFibroblast growth factorCrystallographyFibroblast growth factor receptorBiologyCell biologyCancer cell
153Publications
44H-index
4,499Citations
Publications 152
Newest
#1Malgorzata Zakrzewska (UWr: University of Wrocław)H-Index: 17
#2Daniel Krowarsch (UWr: University of Wrocław)H-Index: 20
Last. Jacek Otlewski (UWr: University of Wrocław)H-Index: 44
view all 5 authors...
Fibroblast growth factor 1 (FGF-1) shows strong angiogenic, osteogenic and tissue-injury repair properties that might be relevant to medical applications. Since FGF-1 is partially unfolded at physiological temperature we decided to increase significantly its conformational stability and test how such an improvement will affect its biological function. Using an homology approach and rational strategy we designed two new single FGF-1 mutations: Q40P and S47I that appeared to be the most strongly s...
94 CitationsSource
#1Jacek Otlewski (UWr: University of Wrocław)H-Index: 44
#2Filip Jelen (UWr: University of Wrocław)H-Index: 13
Last. Arkadiusz Oleksy (UWr: University of Wrocław)H-Index: 6
view all 4 authors...
Proteases and their natural protein inhibitors are among the most intensively studied protein–protein complexes. There are about 30 structurally distinct inhibitor families that are able to block serine, cysteine, metallo- and aspartyl proteases. The mechanisms of inhibition can be related to the catalytic mechanism of protease action or include a mechanism-unrelated steric blockage of the active site or its neighborhood. The structural elements that are responsible for the inhibition most often...
119 CitationsSource
#1Jacek OtlewskiH-Index: 44
#1Jacek OtlewskiH-Index: 5
Last. Arkadiusz OleksyH-Index: 6
view all 3 authors...
Proteases and their natural protein inhibitors are among the most intensively studied protein–protein complexes. There are about 30 structurally distinct inhibitor families that are able to block serine, cysteine, metalloand aspartyl proteases. The mechanisms of inhibition can be related to the catalytic mechanism of protease action or include a mechanism-unrelated steric blockage of the active site or its neighborhood. The structural elements that are responsible for the inhibition most often i...
#1Honorata Czapinska (UWr: University of Wrocław)H-Index: 18
#1Honorata Czapinska (UWr: University of Wrocław)H-Index: 7
Last. Jacek Otlewski (UWr: University of Wrocław)H-Index: 44
view all 4 authors...
The bovine chymotrypsin–bovine pancreatic trypsin inhibitor (BPTI) interaction belongs to extensively studied models of protein–protein recognition. The accommodation of the inhibitor P1 residue in the S1 binding site of the enzyme forms the hot spot of this interaction. Mutations introduced at the P1 position of BPTI result in a more than five orders of magnitude difference of the association constant values with the protease. To elucidate the structural aspects of the discrimination between di...
12 CitationsSource
#1Urszula Derewenda (UVA: University of Virginia)H-Index: 41
#2Arkadiusz Oleksy (UWr: University of Wrocław)H-Index: 6
Last. Zygmunt S. Derewenda (UVA: University of Virginia)H-Index: 66
view all 9 authors...
Abstract Calcium sensitization in smooth muscle is mediated by the RhoA GTPase, activated by hitherto unspecified nucleotide exchange factors (GEFs) acting downstream of Gαq/Gα 12/13 trimeric G proteins. Here, we show that at least one potential GEF, the PDZRhoGEF, is present in smooth muscle, and its isolated DH/PH fragment induces calcium sensitization in the absence of agonist-mediated signaling. In vitro, the fragment shows high selectivity for the RhoA GTPase. Full-length fragment is requir...
106 CitationsSource
#1Malgorzata Zakrzewska (UWr: University of Wrocław)H-Index: 17
#2Daniel Krowarsch (UWr: University of Wrocław)H-Index: 20
Last. Jacek Otlewski (UWr: University of Wrocław)H-Index: 44
view all 4 authors...
Fibroblast growth factor 1 is a powerful mitogen playing an important role in morphogenesis, angiogenesis and wound healing and is therefore of potential medical interest. Using homologous sequence and structure comparisons, we designed and constructed 16 mutants of FGF-1 with increased thermodynamic stability, as determined by chemical and heat denaturation. For multiple mutants, additive effects on stability were observed, providing mutants up to 7.8°C more stable than the wild-type. None of t...
80 CitationsSource
#1Dominika BorekH-Index: 29
#2Karolina MichalskaH-Index: 16
Last. Mariusz Jaskolski (PAN: Polish Academy of Sciences)H-Index: 51
view all 9 authors...
We describe the expression, purification, and biochemical characterization of two homologous enzymes, with amidohydrolase activities, of plant (Lupinus luteus potassium-independent asparaginase, LlA) and bacterial (Escherichia coli, ybiK/spt/iaaA gene product, EcAIII) origin. Both enzymes were expressed in E. coli cells, with (LlA) or without (EcAIII) a His-tag sequence. The proteins were purified, yielding 6 or 30 mg·L−1 of culture, respectively. The enzymes are heat-stable up to 60 °C and show...
64 CitationsSource
#1Myung Hee Kim (UVA: University of Virginia)H-Index: 31
#2David R. Cooper (UVA: University of Virginia)H-Index: 19
Last. Zygmunt S. Derewenda (UVA: University of Virginia)H-Index: 66
view all 8 authors...
Abstract Mutations in the Lis1 gene result in lissencephaly (smooth brain), a debilitating developmental syndrome caused by the impaired ability of postmitotic neurons to migrate to their correct destination in the cerebral cortex. Sequence similarities suggest that the LIS1 protein contains a C-terminal seven-blade β-propeller domain, while the structure of the N-terminal fragment includes the LisH (Lis-homology) motif, a pattern found in over 100 eukaryotic proteins with a hitherto unknown fun...
105 CitationsSource
#1Ronny Helland (University of Tromsø)H-Index: 19
#2Honorata Czapinska (UWr: University of Wrocław)H-Index: 18
Last. Arne O. Smalås (University of Tromsø)H-Index: 27
view all 6 authors...
Abstract Crystal structures of P1 Gly, Val, Leu and Phe bovine pancreatic trypsin inhibitor (BPTI) variants in complex with two serine proteinases, bovine trypsin and chymotrypsin, have been determined. The association constants for the four mutants with the two enzymes show that the enlargement of the volume of the P1 residue is accompanied by an increase of the binding energy, which is more pronounced for bovine chymotrypsin. Since the conformation of the P1 side-chains in the two S1 pockets i...
10 CitationsSource
#1Hanna-Kirsti S. Leiros (University of Tromsø)H-Index: 23
#2Bjørn Olav Brandsdal (University of Tromsø)H-Index: 24
Last. Arne O. Smalås (University of Tromsø)H-Index: 27
view all 9 authors...
The variation in inhibitor specificity for five different amine inhibitors bound to CST, BT, and the cold-adapted AST has been studied by use of association constant measurements, structural analysis of high-resolution crystal structures, and the LIE method. Experimental data show that AST binds the 1BZA and 2BEA inhibitors 0.8 and 0.5 kcal/mole more strongly than BT. However, structural interactions and orientations of the inhibitors within the S1 site have been found to be virtually identical ...
103 CitationsSource