7JZU

SARS-CoV-2 spike in complex with LCB1 (local refinement of the RBD and LCB1)

7JZU の概要

• エントリーDOI: 10.2210/pdb7jzu/pdb
• EMDBエントリー: 22574
• 分子名称: LCB1, Spike glycoprotein, 2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-[alpha-L-fucopyranose-(1-6)]2-acetamido-2-deoxy-beta-D-glucopyranose (3 entities in total)
• 機能のキーワード: sars-cov-2, covid-19, spike glycoprotein, fusion protein, neutralizing antibodies, structural genomics, seattle structural genomics center for infectious disease, ssgcid, inhibotor, viral protein
• 由来する生物種: synthetic construct; 詳細
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 150164.11

構造登録者

Park, Y.J.,Veesler, D.,Seattle Structural Genomics Center for Infectious Disease (SSGCID) (登録日: 2020-09-02, 公開日: 2020-09-23, 最終更新日: 2024-10-23)

主引用文献

Cao, L.,Goreshnik, I.,Coventry, B.,Case, J.B.,Miller, L.,Kozodoy, L.,Chen, R.E.,Carter, L.,Walls, A.C.,Park, Y.J.,Strauch, E.M.,Stewart, L.,Diamond, M.S.,Veesler, D.,Baker, D.
De novo design of picomolar SARS-CoV-2 miniprotein inhibitors.
Science, 370:426-431, 2020

PubMed Abstract: Targeting the interaction between the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike protein and the human angiotensin-converting enzyme 2 (ACE2) receptor is a promising therapeutic strategy. We designed inhibitors using two de novo design approaches. Computer-generated scaffolds were either built around an ACE2 helix that interacts with the spike receptor binding domain (RBD) or docked against the RBD to identify new binding modes, and their amino acid sequences were designed to optimize target binding, folding, and stability. Ten designs bound the RBD, with affinities ranging from 100 picomolar to 10 nanomolar, and blocked SARS-CoV-2 infection of Vero E6 cells with median inhibitory concentration (IC) values between 24 picomolar and 35 nanomolar. The most potent, with new binding modes, are 56- and 64-residue proteins (IC ~ 0.16 nanograms per milliliter). Cryo-electron microscopy structures of these minibinders in complex with the SARS-CoV-2 spike ectodomain trimer with all three RBDs bound are nearly identical to the computational models. These hyperstable minibinders provide starting points for SARS-CoV-2 therapeutics.

PubMed: 32907861
DOI: 10.1126/science.abd9909

実験手法

ELECTRON MICROSCOPY (3.1 Å)