Three-dimensional structure of human cyclooxygenase (hCOX)-1

The beneficial effects of Cyclooxygenases (COX) inhibitors on human health have been known for thousands of years. Nevertheless, COXs, particularly COX-1, have been linked to a plethora of human diseases such as cancer, heart failure, neurological and neurodegenerative diseases only recently. COXs catalyze the first step in the biosynthesis of prostaglandins (PGs) and are among the most important mediators of inflammation. All published structural work on COX-1 deals with the ovine isoenzyme, which is easier to produce in milligram-quantities than the human enzyme and crystallizes readily. Here, we report the long-sought structure of the human cyclooxygenase-1 (hCOX-1) that we refined to an R/Rfree of 20.82/26.37, at 3.36 Å resolution. hCOX-1 structure provides a detailed picture of the enzyme active site and the residues crucial for inhibitor/substrate binding and catalytic activity. We compared hCOX-1 crystal structure with the ovine COX-1 and human COX-2 structures by using metrics based on Cartesian coordinates, backbone dihedral angles, and solvent accessibility coupled with multivariate methods. Differences and similarities among structures are discussed, with emphasis on the motifs responsible for the diversification of the various enzymes (primary structure, stability, catalytic activity, and specificity). The structure of hCOX-1 represents an essential step towards the development of new and more selective COX-1 inhibitors of enhanced therapeutic potential

Performance studies of the CMS strip tracker before installation

Peer reviewe

CMS physics technical design report : Addendum on high density QCD with heavy ions

Peer reviewe

Strategie di densificazione dei paesaggi intermedi nella Puglia centrale

I dati sul consumo di suolo evidenziano molteplici modalità di impiego delle risorse territoriali delle espansioni insediative recenti, in relazione a modelli storicizzati di insediamento. Per affrontare i temi connessi al progetto della città contemporanea è utile interrogarsi sulle posture cognitivo-interpretative che guardano i sistemi urbani come parti inscindibili dal proprio territorio rurale, e legate da un ‘paesaggio intermedio’. La riqualificazione delle frange urbane si fonda su tale prospettiva bidirezionale, misurando le strategie di densificazione del paesaggio di confine in contesti urbani con una morfologia compatta e tassi contenuti di dispersione insediativa. Il caso preso in esame è quello della Puglia centrale anche alla luce degli approfondimenti del nuovo Piano Paesaggistico Territoriale Regionale