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Dynamic characterisation of the netrin-like domain of human type 1 procollagen C-proteinase enhancer and comparison to the N-terminal domain of tissue inhibitor of metalloproteinases (TIMP)

By Richard A. Williamson, Parthena Panagiotidou, Joni D. Mott and Mark J. Howard

Abstract

The backbone mobility of the C-terminal domain of procollagen C-proteinase enhancer (NTR(PCOLCE1)), part of a connective tissue glycoprotein, was determined using (15)N NMR spectroscopy. NTR(PCOLCE1) has been shown to be a netrin-like domain and adopts an OB-fold such as that found in the N-terminal domain of tissue inhibitors of metalloproteinases-1 (N-TIMP-1), N-TIMP-2, the laminin-binding domain of agrin and the C-terminal domain of complement protein C5. NMR relaxation dynamics of NTR(PCOLCE1) highlight conformational flexibility in the N-terminus, strand A and the proximal CD loop. This region in N-TIMP is known to be essential for inhibitory activity against the matrix metalloproteinases and suggests that this region is of equal importance for NTR(PCOLCE1), although the specific functional activity of the NTR(PCOLCE1) domain is still unknown. Dynamics observed within the structural core of NTR(PCOLCE1) that are not observed in N-TIMP molecules suggest that although the two domains have a similar architecture, the NTR(PCOLCE1) domain will show different thermodynamic properties on binding and hence the target molecule could be somewhat different from that observed for the TIMPs. ModelFree order parameters show that NTR(PCOLCE1) has more flexibility than both N-TIMP-1 and N-TIMP-2

Topics: QD, QH301
Year: 2008
DOI identifier: 10.1039/b717901d
OAI identifier: oai:kar.kent.ac.uk:5325
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