2AYK

INHIBITOR-FREE CATALYTIC FRAGMENT OF HUMAN FIBROBLAST COLLAGENASE, NMR, MINIMIZED AVERAGE STRUCTURE

Summary for 2AYK

• Entry DOI: 10.2210/pdb2ayk/pdb
• Descriptor: COLLAGENASE, ZINC ION, CALCIUM ION (3 entities in total)
• Functional Keywords: matrix metalloproteinase, hydrolase, metalloprotease, glycoprotein
• Biological source: Homo sapiens (human)
• Cellular location: Secreted, extracellular space, extracellular matrix (Probable): P03956
• Total number of polymer chains: 1
• Total formula weight: 19036.44

Authors

Powers, R.,Moy, F.J. (deposition date: 1997-11-06, release date: 1998-02-25, Last modification date: 2024-05-22)

Primary citation

Moy, F.J.,Chanda, P.K.,Cosmi, S.,Pisano, M.R.,Urbano, C.,Wilhelm, J.,Powers, R.
High-resolution solution structure of the inhibitor-free catalytic fragment of human fibroblast collagenase determined by multidimensional NMR.
Biochemistry, 37:1495-1504, 1998

PubMed Abstract: The high-resolution solution structure of the inhibitor-free catalytic fragment of human fibroblast collagenase (MMP-1), a protein of 18.7 kDa, which is a member of the matrix metalloproteinase family, has been determined using three-dimensional heteronuclear NMR spectroscopy. A total of 30 structures were calculated by means of hybrid distance geometry-simulated annealing using a total of 3333 experimental NMR restraints, consisting of 2409 approximate interproton distance restraints, 84 distance restraints for 42 backbone hydrogen bonds, 426 torsion angle restraints, 125 3JNH alpha restraints, 153 C alpha restraints, and 136 C beta restraints. The atomic rms distribution about the mean coordinate positions for the 30 structures for residues 7-137 and 145-163 is 0.42 +/- 0.04 A for the backbone atoms, 0.80 +/- 0.04 A for all atoms, and 0.50 +/- 0.03 A for all atoms excluding disordered side chains. The overall structure of MMP-1 is composed of a beta-sheet consisting of five beta-strands in a mixed parallel and anti-parallel arrangement and three alpha-helices. A best-fit superposition of the NMR structure of inhibitor-free MMP-1 with the 1.56 A resolution X-ray structure by Spurlino et al. [Spurlino, J. C., Smallwood, A. M., Carlton, D. D., Banks, T. M., Vavra, K. J., Johnson, J. S., Cook, E. R., Falvo, J., and Wahl, R. C., et al. (1994) Proteins: Struct., Funct., Genet. 19, 98-109] complexed with a hydroxamate inhibitor yields a backbone atomic rms difference of 1.22 A. The majority of differences between the NMR and X-ray structure occur in the vicinity of the active site for MMP-1. This includes an increase in mobility for residues 138-144 and a displacement for the Ca(2+)-loop (residues 74-80). Distinct differences were observed for side-chain torsion angles, in particular, the chi 1 for N80 is -60 degrees in the NMR structure compared to 180 degrees in the X-ray. This results in the side chain of N80 occupying and partially blocking access to the active site of MMP-1.

PubMed: 9484219
DOI: 10.1021/bi972181w

Experimental method

SOLUTION NMR