Institution
University of Florence
Education•Florence, Toscana, Italy•
About: University of Florence is a education organization based out in Florence, Toscana, Italy. It is known for research contribution in the topics: Population & Carbonic anhydrase. The organization has 27292 authors who have published 79599 publications receiving 2341684 citations. The organization is also known as: Università degli studi di Firenze & Universita degli studi di Firenze.
Papers published on a yearly basis
Papers
More filters
••
TL;DR: Dissection of the protein into six peptides corresponding to different regions of the sequence indicates that the kinetic partitioning between aggregation and folding can be attributed to the intrinsic conformational preferences of the denatured polypeptide chain.
Abstract: We have systematically studied the effects of 40 single point mutations on the conversion of the denatured form of the α/β protein acylphosphatase (AcP) into insoluble aggregates. All the mutations that significantly perturb the rate of aggregation are located in two regions of the protein sequence, residues 16–31 and 87–98, each of which has a relatively high hydrophobicity and propensity to form β-sheet structure. The measured changes in aggregation rate upon mutation correlate with changes in the hydrophobicity and β-sheet propensity of the regions of the protein in which the mutations are located. The two regions of the protein sequence that determine the aggregation rate are distinct from those parts of the sequence that determine the rate of protein folding. Dissection of the protein into six peptides corresponding to different regions of the sequence indicates that the kinetic partitioning between aggregation and folding can be attributed to the intrinsic conformational preferences of the denatured polypeptide chain.
423 citations
••
TL;DR: An unexpected nanomolar affinity is demonstrated of the COX-2 specific arylsulfonamide-type celecoxib and valdecoxib for isoenzymes of the totally unrelated carbonic anhydrase (CA) family, such as CA I, II, IV, and IX, whereas the rofecoxib methyl sulfone-type has no effect.
Abstract: By optimizing binding to a selected target protein, modern drug research strives to develop safe and efficacious agents for the treatment of disease. Selective drug action is intended to minimize undesirable side effects from scatter pharmacology. Celecoxib (Celebrex), valdecoxib (Bextra), and rofecoxib (Vioxx) are nonsteroidal antiinflammatory drugs (NSAIDs) due to selective inhibition of inducible cyclooxygenase COX-2 while sparing inhibition of constitutive COX-1. While rofecoxib contains a methyl sulfone constituent, celecoxib and valdecoxib possess an unsubstituted arylsulfonamide moiety. The latter group is common to many carbonic anhydrase (CA) inhibitors. Using enzyme kinetics and X-ray crystallography, we demonstrate an unexpected nanomolar affinity of the COX-2 specific arylsulfonamide-type celecoxib and valdecoxib for isoenzymes of the totally unrelated carbonic anhydrase (CA) family, such as CA I, II, IV, and IX, whereas the rofecoxib methyl sulfone-type has no effect. When administered orally to glaucomatous rabbits, celecoxib and valdecoxib lowered intraocular pressure, suggesting that these agents may have utility in the treatment of this disorder. The crystal structure of celecoxib in complex with CA II reveals part of this inhibition to be mediated via binding of the sulfonamide group to the catalytic zinc of CA II. To investigate the structural basis for cross-reactivity of these compounds between COX-2 and CA II, we compared the molecular recognition properties of both protein binding pockets in terms of local physicochemical similarities among binding site-exposed amino acids accommodating different portions of the drug molecules. Our approach Cavbase, implemented into Relibase, detects similarities between the sites, suggesting some potential to predict unexpected cross-reactivity of drugs among functionally unrelated target proteins. The observed cross-reactivity with CAs may also contribute to differences in the pharmacological profiles, in particular with respect to glaucoma and anticancer therapy and may suggest new opportunities of these COX-2 selective NSAIDs.
423 citations
••
TL;DR: The role of smoking as an independent predictor of clinical, surgical, and endoscopic recurrence in Crohn's disease is evaluated.
422 citations
••
Durham University1, University of Helsinki2, University of Wisconsin-Madison3, University of Rochester4, University of Catania5, Weizmann Institute of Science6, University of Warsaw7, University of Southampton8, CERN9, Lawrence Livermore National Laboratory10, Indian Institute of Science11, University of Montpellier12, Spanish National Research Council13, University of Zurich14, ETH Zurich15, Stanford University16, Northwestern University17, University of Pittsburgh18, Carleton University19, University of Hamburg20, Moscow State University21, University of Florida22, Paul Scherrer Institute23, University of Würzburg24, Imperial College London25, Florida State University26, University of Florence27, University of Bonn28, University at Buffalo29, RWTH Aachen University30, University of Sheffield31, University of California, Irvine32, Laboratoire d'Annecy-le-Vieux de physique des particules33, Brookhaven National Laboratory34, Argonne National Laboratory35, University of Bergen36, University of Mainz37, Centers for Medicare and Medicaid Services38, Lancaster University39, University of California, Santa Cruz40, University of Copenhagen41, University of Tokyo42, Austrian Academy of Sciences43, University of Manchester44, University College London45, University of Edinburgh46, University of California, Davis47, University of California, Berkeley48, University of Glasgow49, University of Barcelona50, Max Planck Society51, University of Chicago52, University of Turin53, Royal Holloway, University of London54, Kobe University55, University of Oslo56, Kyoto University57
TL;DR: In this paper, the authors discuss the possible interplay between the Large Hadron Collider (LHC) and the International e(+)e(-) Linear Collider (ILC) in testing the Standard Model and in discovering and determining the origin of new physics.
422 citations
••
TL;DR: A new view of protein biology underscores the key importance of the negative selection against molecules with significant tendency to aggregate as well as of the development of the complex molecular machineries aimed at hindering the appearance of misfolded proteins and their toxic early aggregates.
422 citations
Authors
Showing all 27699 results
Name | H-index | Papers | Citations |
---|---|---|---|
Charles A. Dinarello | 190 | 1058 | 139668 |
D. M. Strom | 176 | 3167 | 194314 |
Gregory Y.H. Lip | 169 | 3159 | 171742 |
Christopher M. Dobson | 150 | 1008 | 105475 |
Dirk Inzé | 149 | 647 | 74468 |
Thomas Hebbeker | 148 | 1984 | 114004 |
Marco Zanetti | 145 | 1439 | 104610 |
Richard B. Devereux | 144 | 962 | 116403 |
Gunther Roland | 141 | 1471 | 100681 |
Markus Klute | 139 | 1447 | 104196 |
Tariq Aziz | 138 | 1646 | 96586 |
Guido Tonelli | 138 | 1458 | 97248 |
Giorgio Trinchieri | 138 | 433 | 78028 |
Christof Roland | 137 | 1308 | 96632 |
Christoph Paus | 137 | 1585 | 100801 |