User:Dora Bonadio/Sandbox 1: Difference between revisions

The M^pro is a protein of approximately 30 kDa <ref name="replication" /><ref name="ofmpro">Jin, Zhenming, Xiaoyu Du, Yechun Xu, Yongqiang Deng, Meiqin Liu, Yao Zhao, Bing Zhang, et al. 2020. ‘Structure of M pro from SARS-CoV-2 and Discovery of Its Inhibitors’. Nature, April, 1–5. https://doi.org/10.1038/s41586-020-2223-y. </ref> consisting of <scene name='84/845941/Assembly/3'>two protomers</scene> containing 306 amino acid residues each <ref name="Crystal_structure" />. This protomers dimerize forming a homodimer <ref name="Crystal_structure" />. Each protomer consists of <scene name='84/845941/Domains/1'>three domains</scene>: I (<scene name='84/845941/Domaini/1'>chymotrypsin-like</scene>; residues 10-99), II (<scene name='84/845941/Domains2/1'>picornavirus 3C protease-like</scene>; residues 100-182), and III (<scene name='84/845941/Domains3/1'>a globular cluster</scene>; residues 198-303). Domains I and II comprise six-stranded antiparallel β-barrels and domain III comprises five α-helices <ref name="Crystal_structure" /><ref name="ofmpro" />. The substrate-binding site is located between domains I and II with the <scene name='84/845941/Catalyticsite/1'>catalytic site</scene> containing the amino acid residues Cys145 and His41 <ref name="Crystal_structure" />. Domain III, in turn, has been shown to be involved in the regulation of M^pro dimerization, what is necessary for the catalytic activity of this enzyme once it helps to shape the substrate-binding site <ref name="Crystal_structure" /><ref name="reveals"> PMID:12093723</ref>.  

As mentioned above, SARS-CoV-2 M^pro has 96% sequence identity with SARS-CoV M^pro and as expected, also a highly similar three-dimensional structure <ref name="Crystal_structure" />. Indeed, it has been shown that the substrate-binding pocket is a highly conserved region of M^pro among an important number of CoV M^pro <ref name="ofmpro" />. However, an interesting difference found between SARS-CoV M^pro and SARS-CoV-2 M^pro is that in the first one there is a polar interaction between the domains III of each protomer, involving the residues Thr285, what is not found in the COVID-19 virus M^pro <ref name="Crystal_structure" />. In fact, in SARS-CoV-2, the threonine is replaced by <scene name='84/845941/Ala285/1'>alanine</scene>, leading to a higher proximity between the two domains III of the dimer <ref name="Crystal_structure" />.