High-resolution structure of a retroviral protease folded as a monomer

0369861 - ÚOCHB 2012 RIV DK eng J - Journal Article
Gilski, M. - Kazmierczyk, M. - Krzywda, S. - Zábranská, Helena - Cooper, S. - Popovic, Z. - Khatíb, F. - Dímaio, F. - Thompson, J. - Baker, D. - Pichová, Iva - Jaskolski, M.
High-resolution structure of a retroviral protease folded as a monomer.
Acta Crystallographica Section D-Biological Crystallography. D67, č. 11 (2011), s. 907-914. ISSN 0907-4449
R&D Projects: GA MŠMT 1M0508
Institutional research plan: CEZ:AV0Z40550506
Keywords : M-PMV protease * crystal structure * monomer * dimerization inhibitors
Subject RIV: CE - Biochemistry
Impact factor: 12.619, year: 2011

Biophysical and NMR studies of M-PMV protease have indicated that in the absence of substrates or inhibitors M-PMV PR should fold into a stable monomer, but the crystal structure of this protein could not be solved by molecular replacement despite countless attempts. The solution was obtained in mr-rosetta using a model constructed by players of the game Foldit. The structure shows a monomeric protein, with the N- and C-termini completely disordered. The flap loop has an unusual curled shape and a different orientation from both the open and closed states known from dimeric retropepsins. This structure provides important information for the design of dimerization inhibitors of retroviral proteases.
Permanent Link: http://hdl.handle.net/11104/0006760