Solution Strucure of the Active Domain of Tissue Inhitor of Metalloprotrinases.2.A new Member of the OB Fold Protein Family

Williamson, Richard A. and Martorell, Gabriel and Carr, Mark D. and Murphy, Gillian and Docherty, Andrew J. P. and Freedman, Robert B. and Feeney, James (1994) Solution Strucure of the Active Domain of Tissue Inhitor of Metalloprotrinases.2.A new Member of the OB Fold Protein Family. Biochemistry, 33 (39). pp. 11745-11759. ISSN 0006-2960. (The full text of this publication is not available from this repository)

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Official URL
http://dx.doi.org/10.1021/bi00205a010

Abstract

Homonuclear two-dimensional and three-dimensional H-1 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 coil 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.

Item Type: Article
Additional information: 0006-2960 (Print) Comparative Study Journal Article Research Support, Non-U.S. Gov't
Uncontrolled keywords: Amino Acid Sequence Binding Sites Magnetic Resonance Spectroscopy/methods Metalloendopeptidases/antagonists & inhibitors Models, Molecular Molecular Sequence Data Peptide Fragments/*chemistry Protein Conformation *Protein Structure, Secondary Proteins/*chemistry/classification Recombinant Proteins/chemistry Sequence Homology, Amino Acid Solutions/chemistry Tissue Inhibitor of Metalloproteinase-2
Subjects: Q Science > QP Physiology (Living systems) > QP517 Biochemistry
Divisions: Faculties > Science Technology and Medical Studies > School of Biosciences
Depositing User: P. Ogbuji
Date Deposited: 09 Jun 2009 14:43
Last Modified: 29 May 2014 15:56
Resource URI: http://kar.kent.ac.uk/id/eprint/20106 (The current URI for this page, for reference purposes)
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