4x9p
Crystal structure of bovine Annexin A2Crystal structure of bovine Annexin A2
Structural highlights
FunctionANXA2_BOVIN Calcium-regulated membrane-binding protein whose affinity for calcium is greatly enhanced by anionic phospholipids. It binds two calcium ions with high affinity. Publication Abstract from PubMedThe progression of aggressive cancer occurs via angiogenesis and metastasis making these processes important targets for the development of anti-cancer agents. However, recent studies have raised the concern that selective inhibition of angiogenesis results in a switch towards increased tumour growth and metastasis. Since Annexin A2 (AnxA2) is involved in both angiogenesis and metastasis, it may serve as an ideal target for the simultaneous inhibition of both processes. Based on the discovery that domains I (DI) and IV (DIV) of AnxA2 are potent inhibitors of angiogenesis, we designed seven peptides derived from these domains based on AnxA2 crystal structures. The peptides were expressed as fusion peptides to increase their folding and solubility. Light scattering, far-UV circular dichroism and thermal transition analyses were employed to investigate their aggregation tendencies, alpha-helical propensity and stability, respectively. 2,2,2-trifluoroethanol (50%) increased the alpha-helical propensities of all peptides, indicating that they may favour a hydrophobic environment, but did not enhance their thermal stability. DI-P2 appears to be the most stable and folded peptide in a hydrophilic environment. The secondary structure of DI-P2 was confirmed by nuclear magnetic resonance spectra. The effect of the seven AnxA2 peptides on the formation and integrity of capillary-like networks was studied in a co-culture system mimicking many of the angiogenesis-related processes. Notably, DI-P2 inhibited significantly network formation in this system, indicating that the folded DI-P2 peptide interferes with vascular endothelial growth factor-dependent pro-angiogenic processes. Thus, this peptide has the potential of being developed further as an anti-angiogenic drug. The Native Structure of Annexin A2 Peptides in Hydrophilic Environment Determines their Anti-Angiogenic Effects.,Raddum AM, Hollas H, Shumilin I, Henklein P, Kretsinger R, Fossen T, Vedeler A Biochem Pharmacol. 2015 Mar 12. pii: S0006-2952(15)00132-X. doi:, 10.1016/j.bcp.2015.02.013. PMID:25772737[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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