1lvo
From Proteopedia
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Structure of coronavirus main proteinase reveals combination of a chymotrypsin fold with an extra alpha-helical domain
Overview
The key enzyme in coronavirus polyprotein processing is the viral main, proteinase, M(pro), a protein with extremely low sequence similarity to, other viral and cellular proteinases. Here, the crystal structure of the, 33.1 kDa transmissible gastroenteritis (corona)virus M(pro) is reported., The structure was refined to 1.96 A resolution and revealed three dimers, in the asymmetric unit. The mutual arrangement of the protomers in each of, the dimers suggests that M(pro) self-processing occurs in trans. The, active site, comprised of Cys144 and His41, is part of a chymotrypsin-like, fold that is connected by a 16 residue loop to an extra domain featuring a, novel alpha-helical fold. Molecular modelling and mutagenesis data, implicate the loop in substrate binding and elucidate S1 and S2 subsites, suitable to accommodate the side chains of the P1 glutamine and P2 leucine, residues of M(pro) substrates. Interactions involving the N-terminus and, the alpha-helical domain stabilize the loop in the orientation required, for trans-cleavage activity. The study illustrates that RNA viruses have, evolved unprecedented variations of the classical chymotrypsin fold.
About this Structure
1LVO is a Single protein structure of sequence from Transmissible gastroenteritis virus with SO4, DIO and MRD as ligands. Full crystallographic information is available from OCA.
Reference
Structure of coronavirus main proteinase reveals combination of a chymotrypsin fold with an extra alpha-helical domain., Anand K, Palm GJ, Mesters JR, Siddell SG, Ziebuhr J, Hilgenfeld R, EMBO J. 2002 Jul 1;21(13):3213-24. PMID:12093723
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