1EUB

SOLUTION STRUCTURE OF THE CATALYTIC DOMAIN OF HUMAN COLLAGENASE-3 (MMP-13) COMPLEXED TO A POTENT NON-PEPTIDIC SULFONAMIDE INHIBITOR

Summary for 1EUB

• Entry DOI: 10.2210/pdb1eub/pdb
• Related: 456C 830C
• Descriptor: COLLAGENASE 3, ZINC ION, CALCIUM ION, ... (6 entities in total)
• Functional Keywords: alpha helix, beta sheet, protein-inhibitor complex, hydrolase-hydrolase inhibitor complex, hydrolase/hydrolase inhibitor
• Biological source: Homo sapiens (human)
• Cellular location: Secreted, extracellular space, extracellular matrix (Probable): P45452
• Total number of polymer chains: 1
• Total formula weight: 19843.85

Authors

Zhang, X.,Gonnella, N.C.,Koehn, J.,Pathak, N.,Ganu, V.,Melton, R.,Parker, D.,Hu, S.I.,Nam, K.Y. (deposition date: 2000-04-14, release date: 2001-04-14, Last modification date: 2024-05-22)

Primary citation

Zhang, X.,Gonnella, N.C.,Koehn, J.,Pathak, N.,Ganu, V.,Melton, R.,Parker, D.,Hu, S.I.,Nam, K.Y.
Solution structure of the catalytic domain of human collagenase-3 (MMP-13) complexed to a potent non-peptidic sulfonamide inhibitor: binding comparison with stromelysin-1 and collagenase-1.
J.Mol.Biol., 301:513-524, 2000

PubMed Abstract: The full three-dimensional structure of the catalytic domain of human collagenase-3 (MMP-13) complexed to a potent, sulfonamide hydroxamic acid inhibitor (CGS 27023) has been determined by NMR spectroscopy. The results reveal a core domain for the protein consisting of three alpha-helices and five beta-sheet strands with an overall tertiary fold similar to the catalytic domains of other matrix metalloproteinase family members. The S1' pocket, which is the major site of hydrophobic binding interaction, was found to be a wide cleft spanning the length of the protein and presenting facile opportunity for inhibitor extension deep into the pocket. Comparison with the reported X-ray structure of collagenase-3 showed evidence of flexibility for the loop region flanking the S1' pocket in both NMR and X-ray data. This flexibility was corroborated by NMR dynamics studies. Inhibitor binding placed the methoxy phenyl ring in the S1' pocket with the remainder of the molecule primarily solvent-exposed. The binding mode for this inhibitor was found to be similar with respect to stromelysin-1 and collagenase-1; however, subtle comparative differences in the interactions between inhibitor and enzyme were observed for the three MMPs that were consistent with their respective binding potencies.

PubMed: 10926524
DOI: 10.1006/jmbi.2000.3988

Experimental method

SOLUTION NMR