4AYK

CATALYTIC FRAGMENT OF HUMAN FIBROBLAST COLLAGENASE COMPLEXED WITH CGS-27023A, NMR, 30 STRUCTURES

Summary for 4AYK

• Entry DOI: 10.2210/pdb4ayk/pdb
• Descriptor: PROTEIN (COLLAGENASE), ZINC ION, CALCIUM ION, ... (4 entities in total)
• Functional Keywords: matrix metalloproteinase, hydrolase, metalloprotease, glycoprotein
• Biological source: Homo sapiens (human)
• Total number of polymer chains: 1
• Total formula weight: 19429.89

Authors

Powers, R.,Moy, F.J. (deposition date: 1999-02-01, release date: 1999-06-05, Last modification date: 2023-12-27)

Primary citation

Moy, F.J.,Chanda, P.K.,Chen, J.M.,Cosmi, S.,Edris, W.,Skotnicki, J.S.,Wilhelm, J.,Powers, R.
NMR solution structure of the catalytic fragment of human fibroblast collagenase complexed with a sulfonamide derivative of a hydroxamic acid compound.
Biochemistry, 38:7085-7096, 1999

PubMed Abstract: The solution structure of the catalytic fragment of human fibroblast collagenase (MMP-1) complexed with a sulfonamide derivative of a hydroxamic acid compound (CGS-27023A) has been determined using two-dimensional and three-dimensional heteronuclear NMR spectroscopy. The solution structure of the complex was calculated by means of hybrid distance geometry-simulated annealing using a combination of experimental NMR restraints obtained from the previous refinement of the inhibitor-free MMP-1 (1) and recent restraints for the MMP-1:CGS-27023A complex. The hydroxamic acid moiety of CGS-27023A was found to chelate to the "right" of the catalytic zinc where the p-methoxyphenyl sits in the S1' active-site pocket, the isopropyl group is in contact with H83 and N80, and the pyridine ring is solvent exposed. The sulfonyl oxygens are in hydrogen-bonding distance to the backbone NHs of L81 and A82. This is similar to the conformation determined by NMR of the inhibitor bound to stromelysin (2, 3). A total of 48 distance restraints were observed between MMP-1 and CGS-27023A from 3D 13C-edited/12C-filtered NOESY and 3D 15N-edited NOESY experiments. An additional 18 intramolecular restraints were observed for CGS-27023A from a 2D 12C-filtered NOESY experiment. A minimal set of NMR experiments in combination with the free MMP-1 assignments were used to assign the MMP-1 (1)H, 13C, and 15N resonances in the MMP-1:CGS-27023A complex. The assignments of CGS-27023A in the complex were obtained from 2D 12C-filtered NOESY and 2D 12C-filtered TOCSY experiments.

PubMed: 10353819
DOI: 10.1021/bi982576v

Experimental method

SOLUTION NMR