1ayk
INHIBITOR-FREE CATALYTIC FRAGMENT OF HUMAN FIBROBLAST COLLAGENASE, NMR, 30 STRUCTURES
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OverviewOverview
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.
About this StructureAbout this Structure
1AYK is a Single protein structure of sequence from Homo sapiens with ZN and CA as ligands. Active as Interstitial collagenase, with EC number 3.4.24.7 Structure known Active Sites: CAB, ZNA and ZNB. Full crystallographic information is available from OCA.
ReferenceReference
High-resolution solution structure of the inhibitor-free catalytic fragment of human fibroblast collagenase determined by multidimensional NMR., Moy FJ, Chanda PK, Cosmi S, Pisano MR, Urbano C, Wilhelm J, Powers R, Biochemistry. 1998 Feb 10;37(6):1495-504. PMID:9484219
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