PDB 2W0D deposited: 2008-08-13 modified: 2011-12-28
Title Does a Fast Nuclear Magnetic Resonance Spectroscopy- and X-Ray Crystallography Hybrid Approach Provide Reliable Structural Information of Ligand-Protein Complexes? A Case Study of Metalloproteinases.
Authors Agback, T., Bertini, I., Derbyshire, D.J., Felli, I.C., Isaksson, J., Kovacs, H., Nystrom, S., Wallberg, H.
Structure factors resolution 2.0 rfactor 0.17868 rfree 0.23683
DPI 0.42 theoretical min: 0.19

A human matrix metalloproteinase (MMP) hydroxamic acid inhibitor (CGS27023A) was cross-docked into 15 MMP-12, MMP-13, MMP-9, and MMP-1 cocrystal structures. The aim was to validate a fast protocol for ligand binding conformation elucidation and to probe the feasibility of using inhibitor-protein NMR contacts to dock an inhibitor into related MMP crystal structures. Such an approach avoids full NMR structure elucidation, saving both spectrometer- and analysis time. We report here that for the studied MMPs, one can obtain docking results well within 1 A compared to the corresponding reference X-ray structure, using backbone amide contacts only. From the perspective of the pharmaceutical industry, these results are relevant for the binding studies of inhibitor series to a common target and have the potential advantage of obtaining information on protein-inhibitor complexes that are difficult to crystallize.

J.Med.Chem. 2009 Mar; 52(6):1712- doi:10.1021/JM801388Q

Cross References
Database source Identifier Description
PubMed 19239231 JMCMAR
Biomolecule Structure Assembly Serial Assembly Type Conformational State Chains Ligands Atoms
2W0D/1 2W0D 1 monomer 0 1 10 1399
2W0D/2 2W0D 2 monomer 0 1 6 1356
2W0D/3 2W0D 3 monomer 0 1 10 1357
2W0D/4 2W0D 4 monomer 0 1 10 1350