6Y3C

Human COX-1 Crystal Structure

6Y3C の概要

• エントリーDOI: 10.2210/pdb6y3c/pdb
• 分子名称: Prostaglandin G/H synthase 1, beta-D-mannopyranose-(1-3)-[beta-D-mannopyranose-(1-6)]beta-D-mannopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose, 2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose, ... (5 entities in total)
• 機能のキーワード: cox-1, cyclooxygenase, peroxidase, prostaglandin, heme, oxidoreductase
• 由来する生物種: Homo sapiens (Human)
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 68397.59

構造登録者

Miciaccia, M.,Belviso, B.D.,Iaselli, M.,Ferorelli, S.,Perrone, M.G.,Caliandro, R.,Scilimati, A. (登録日: 2020-02-18, 公開日: 2020-02-26, 最終更新日: 2024-10-16)

主引用文献

Miciaccia, M.,Belviso, B.D.,Iaselli, M.,Cingolani, G.,Ferorelli, S.,Cappellari, M.,Loguercio Polosa, P.,Perrone, M.G.,Caliandro, R.,Scilimati, A.
Three-dimensional structure of human cyclooxygenase (hCOX)-1.
Sci Rep, 11:4312-4312, 2021

PubMed Abstract: 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/R 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.

PubMed: 33619313
DOI: 10.1038/s41598-021-83438-z

実験手法

X-RAY DIFFRACTION (3.361 Å)