Prediction of heparin binding sites in bone morphogenetic proteins (BMPs)
Gandhi, Neha S. & Mancera, Ricardo L. (2012) Prediction of heparin binding sites in bone morphogenetic proteins (BMPs). Biochimica et Biophysica Acta (BBA) - Proteins and Proteomics, 1824(12), pp. 1374-1381.
Heparin is a glycosaminoglycan known to bind bone morphogenetic proteins (BMPs) and the growth and differentiation factors (GDFs) and has strong and variable effects on BMP osteogenic activity. In this paper we report our predictions of the likely heparin binding sites for BMP-2 and 14. The N-terminal sequences upstream of TGF-β-type cysteine-knot domains in BMP-2, 7 and 14 contain the basic residues arginine and lysine, which are key components of the heparin/HS-binding sites, with these residues being highly non-conserved. Importantly, evolutionary conserved surfaces on the beta sheets are required for interactions with receptors and antagonists. Furthermore, BMP-2 has electropositive surfaces on two sides compared to BMP-7 and BMP-14. Molecular docking simulations suggest the presence of high and low affinity binding sites in dimeric BMP-2. Histidines were found to play a role in the interactions of BMP-2 with heparin; however, a pKa analysis suggests that histidines are likely not protonated. This is indicative that interactions of BMP-2 with heparin do not require acidic pH. Taken together, non-conserved amino acid residues in the N-terminus and residues protruding from the beta sheet (not overlapping with the receptor binding sites and the dimeric interface) and not C-terminal are found to be important for heparin–BMP interactions.
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|Item Type:||Journal Article|
|Keywords:||Heparin; Bone morphogenetic protein (BMP); Growth and differentiation factor (GDF); Transforming growth factor-β (TGF-β); Docking|
|Divisions:||Current > Schools > School of Mathematical Sciences
Current > QUT Faculties and Divisions > Science & Engineering Faculty
|Copyright Owner:||Copyright 2012 Elsevier B.V.|
|Deposited On:||31 Mar 2016 02:37|
|Last Modified:||01 Apr 2016 00:24|
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