Solution structure of the active domain of tissue inhibitor of metalloproteinases-2. A new member of the OB fold protein family
Homonuclear two-dimensional and three-dimensional 1H nuclear magnetic resonance spectroscopy has been used to obtain essentially complete sequence-specific assignments for 123 of the 127 amino acid residues present in the truncated form of tissue inhibitor of metalloproteinases-2 (delta TIMP-2), the...
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Published in | Biochemistry (Easton) Vol. 33; no. 39; pp. 11745 - 11759 |
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Main Authors | , , , , , , |
Format | Journal Article |
Language | English |
Published |
United States
American Chemical Society
04.10.1994
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Subjects | |
Online Access | Get full text |
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Summary: | Homonuclear two-dimensional and three-dimensional 1H nuclear magnetic resonance spectroscopy has been used to obtain essentially complete sequence-specific assignments for 123 of the 127 amino acid residues present in the truncated form of tissue inhibitor of metalloproteinases-2 (delta TIMP-2), the active N-terminal domain of the protein. Analysis of the through-space nuclear Overhauser effect data obtained for delta TIMP-2 allowed determination of both the secondary structure of the domain and also a low-resolution tertiary structure defining the protein backbone topology. The protein contains a five-stranded antiparallel beta-sheet that is rolled over on itself to form a closed beta-barrel, and two short helices which pack close to one another on the same barrel face. A comparison of the delta TIMP-2 structure with other known protein folds reveals that the beta-barrel topology is homologous to that seen in proteins of the oligosaccharide/oligonucleotide binding (OB) fold family. The common structural features include the number of beta-strands and their arrangement, the beta-barrel shear number, an interstrand hydrogen bond network, the packing of the hydrophobic core, and a conserved beta-bulge. Superpositions of the beta-barrels from delta TIMP-2 and two previously known members of the OB protein fold family (staphylococcal nuclease and Escherichia coli heat-labile enterotoxin) confirmed the similarity in beta-barrel topology. The three-dimensional structure of delta TIMP-2 has allowed a more detailed interpretation than was previously possible of the functional significance of available protein sequence and site-directed mutagenesis data for the TIMP family. Furthermore, the structure has revealed conserved surface regions of potential functional importance. |
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Bibliography: | istex:199B83222B13930469271484481811246E705623 ark:/67375/TPS-31JTWR0D-Z |
ISSN: | 0006-2960 1520-4995 |
DOI: | 10.1021/bi00205a010 |