Summary
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.
Method X-RAY DIFFRACTION
Structure factors resolution 2.0 rfactor 0.17868 rfree 0.23683
DPI 0.42 theoretical min: 0.19
Citations

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