2XCN

Crystal structure of HCV NS3 protease with a boronate inhibitor

Summary for 2XCN

• Entry DOI: 10.2210/pdb2xcn/pdb
• Related: 2A4Q 2A4R 2F9U 2XCF
• Descriptor: NS3 PROTEASE, NS4A, N-[(CYCLOPENTYLOXY)CARBONYL]-3-METHYL-L-VALYL-(4R)-N-{(1R)-3-HYDROXY-1-[HYDROXY(OXIDO)BORANYL]PROPYL}-4-(ISOQUINOLIN-1-YLOXY)-L-PROLINAMIDE, ... (6 entities in total)
• Functional Keywords: hydrolase, serine protease
• Biological source: HEPATITIS C VIRUS; More
• Total number of polymer chains: 4
• Total formula weight: 48164.33

Authors

Li, X.,Zhang, Y.-K.,Liu, Y.,Ding, C.Z.,Li, Q.,Zhou, Y.,Plattner, J.J.,Baker, S.J.,Qian, X.,Fan, D.,Liao, L.,Ni, Z.-J.,White, G.V.,Mordaunt, J.E.,Lazarides, L.X.,Slater, M.J.,Jarvest, R.L.,Thommes, P.,Ellis, M.,Edge, C.M.,Hubbard, J.A.,Nassau, P.,McDowell, B.,Skarzynski, T.J.,Rowland, P.,Somers, D.O.,Kazmierski, W.M.,Grimes, R.M.,Wright, L.L.,Smith, G.K.,Zou, W.,Wright, J.,Pennicott, L.E. (deposition date: 2010-04-23, release date: 2010-06-02, Last modification date: 2011-07-13)

Primary citation

Li, X.,Zhang, Y.-K.,Liu, Y.,Ding, C.Z.,Li, Q.,Zhou, Y.,Plattner, J.J.,Baker, S.J.,Qian, X.,Fan, D.,Liao, L.,Ni, Z.-J.,White, G.V.,Mordaunt, J.E.,Lazarides, L.X.,Slater, M.J.,Jarvest, R.L.,Edge, C.M.,Hubbard, J.A.,Nassau, P.,Mcdowell, B.,Skarzynski, T.J.,Thommes, P.,Ellis, M.,Rowland, P.,Somers, D.O.,Kazmierski, W.M.,Grimes, R.M.,Wright, L.L.,Smith, G.K.,Zou, W.,Wright, J.,Pennicott, L.E.
Synthesis and Evaluation of Novel Alpha-Amino Cyclic Boronates as Inhibitors of Hcv Ns3 Protease.
Bioorg.Med.Chem.Lett., 20:3550-, 2010

PubMed Abstract: We have designed and synthesized a novel series of alpha-amino cyclic boronates and incorporated them successfully in several acyclic templates at the P1 position. These compounds are inhibitors of the HCV NS3 serine protease, and structural studies show that they inhibit the NS3 protease by trapping the Ser-139 hydroxyl group in the active site. Synthetic methodologies and SARs of this series of compounds are described.

PubMed: 20493689
DOI: 10.1016/J.BMCL.2010.04.129

Experimental method

X-RAY DIFFRACTION (3.02 Å)