1NSO

Folded monomer of protease from Mason-Pfizer monkey virus

Summary for 1NSO

• Entry DOI: 10.2210/pdb1nso/pdb
• Descriptor: Protease 13 kDa (1 entity in total)
• Functional Keywords: m-pmv, protease, virus maturation, folded monomer, hydrolase
• Biological source: Simian retrovirus SRV-1
• Total number of polymer chains: 1
• Total formula weight: 12189.06

Authors

Veverka, V.,Bauerova, H.,Zabransky, A.,Lang, J.,Ruml, T.,Pichova, I.,Hrabal, R. (deposition date: 2003-01-28, release date: 2003-02-18, Last modification date: 2024-05-22)

Primary citation

Veverka, V.,Bauerova, H.,Zabransky, A.,Lang, J.,Ruml, T.,Pichova, I.,Hrabal, R.
Three-dimensional structure of a monomeric form of a retroviral protease
J.MOL.BIOL., 333:771-780, 2003

PubMed Abstract: The assembly of Mason-Pfizer monkey virus Gag polyproteins into immature capsids and their cleavage by the encoded protease are temporally and spatially separated processes, making the virus a particularly useful model for investigation of protease activation. Here we present a high resolution NMR structure of a fully folded monomer of a 12 kDa M-PMV protease (wt 12 PR) and of a Cys7Ala/Asp26Asn/Cys106Ala mutant (12 PR(D26N/C7A/C106A)). The overall structures of both wt 12 PR and 12 PR(D26N/C7A/C106A) follow the conservative structural motif of other retroviral proteases. The most prominent difference from the canonical fold of retroviral proteases is the absence of the interfacial beta-sheet, which leads to the loss of the principal force stabilizing the dimer of M-PMV PR. The monomer-dimer equilibrium can be shifted in favor of the dimer by adding a substrate or an inhibitor, partially compensating for the missing role of the beta-sheet. We also show that cysteines C7 and C106 play a crucial role in stabilizing the dimer and consequently increasing the proteolytic activity of M-PMV PR. This is consistent with the role of reversible oxidative modification of the cysteine residues in the regulation of the maturation of assembled M-PMV capsids in the cytoplasm.

PubMed: 14568536
DOI: 10.1016/j.jmb.2003.08.049

Experimental method

SOLUTION NMR