2W0D

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.

Summary for 2W0D

• Entry DOI: 10.2210/pdb2w0d/pdb
• Related: 1JIZ 1JK3 1OS2 1OS9 1RMZ 1ROS 1UTT 1UTZ 1Y93 1YCM 1Z3J
• Descriptor: MACROPHAGE METALLOELASTASE, ZINC ION, CALCIUM ION, ... (8 entities in total)
• Functional Keywords: glycoprotein, metal-binding, metalloprotease, secreted, hydrolase, hydroxamate, extracellular matrix, copd, mmp-12, zymogen
• Biological source: HOMO SAPIENS (HUMAN)
• Total number of polymer chains: 4
• Total formula weight: 76337.88

Authors

Isaksson, J.,Nystrom, S.,Derbyshire, D.J.,Wallberg, H.,Agback, T.,Kovacs, H.,Bertini, I.,Felli, I.C. (deposition date: 2008-08-13, release date: 2009-03-03, Last modification date: 2024-05-01)

Primary citation

Isaksson, J.,Nystrom, S.,Derbyshire, D.J.,Wallberg, H.,Agback, T.,Kovacs, H.,Bertini, I.,Felli, I.C.
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.
J.Med.Chem., 52:1712-, 2009

PubMed Abstract: 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.

PubMed: 19239231
DOI: 10.1021/JM801388Q

Experimental method

X-RAY DIFFRACTION (2 Å)