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|1imv, resolution 2.85Å ()|
2.85 A crystal structure of PEDF
Pigment epithelium-derived factor (PEDF), a noninhibitory member of the serpin superfamily, is the most potent inhibitor of angiogenesis in the mammalian ocular compartment. It also has neurotrophic activity, both in the retina and in the central nervous system, and is highly up-regulated in young versus senescent fibroblasts. To provide a structural basis for understanding its many biological roles, we have solved the crystal structure of glycosylated human PEDF to 2.85 A. The structure revealed the organization of possible receptor and heparin-binding sites, and showed that, unlike any other previously characterized serpin, PEDF has a striking asymmetric charge distribution that might be of functional importance. These results provide a starting point for future detailed structure/function analyses into possible mechanisms of PEDF action that could lead to development of therapeutics against uncontrolled angiogenesis.
Crystal structure of human PEDF, a potent anti-angiogenic and neurite growth-promoting factor., Simonovic M, Gettins PG, Volz K, Proc Natl Acad Sci U S A. 2001 Sep 25;98(20):11131-5. Epub 2001 Sep 18. PMID:11562499
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
[PEDF_HUMAN] Defects in SERPINF1 are the cause of osteogenesis imperfecta type 12 (OI12) [MIM:613982]. OI12 is a connective tissue disorder characterized by bone fragility, low bone mass, and recurrent fractures. OI12 is characterized by features compatible with osteogenesis imperfecta type III in the Sillence classification. Patients have normal grayish sclerae and fractures of long bones and severe vertebral compression fractures, with resulting deformities observed as early as the first year of life.
[PEDF_HUMAN] Neurotrophic protein; induces extensive neuronal differentiation in retinoblastoma cells. Potent inhibitor of angiogenesis. As it does not undergo the S (stressed) to R (relaxed) conformational transition characteristic of active serpins, it exhibits no serine protease inhibitory activity.
About this Structure
- Simonovic M, Gettins PG, Volz K. Crystal structure of human PEDF, a potent anti-angiogenic and neurite growth-promoting factor. Proc Natl Acad Sci U S A. 2001 Sep 25;98(20):11131-5. Epub 2001 Sep 18. PMID:11562499 doi:10.1073/pnas.211268598
- ↑ Becker J, Semler O, Gilissen C, Li Y, Bolz HJ, Giunta C, Bergmann C, Rohrbach M, Koerber F, Zimmermann K, de Vries P, Wirth B, Schoenau E, Wollnik B, Veltman JA, Hoischen A, Netzer C. Exome sequencing identifies truncating mutations in human SERPINF1 in autosomal-recessive osteogenesis imperfecta. Am J Hum Genet. 2011 Mar 11;88(3):362-71. doi: 10.1016/j.ajhg.2011.01.015. Epub, 2011 Feb 25. PMID:21353196 doi:10.1016/j.ajhg.2011.01.015
- ↑ Becerra SP, Palmer I, Kumar A, Steele F, Shiloach J, Notario V, Chader GJ. Overexpression of fetal human pigment epithelium-derived factor in Escherichia coli. A functionally active neurotrophic factor. J Biol Chem. 1993 Nov 5;268(31):23148-56. PMID:8226833
- ↑ Becerra SP, Sagasti A, Spinella P, Notario V. Pigment epithelium-derived factor behaves like a noninhibitory serpin. Neurotrophic activity does not require the serpin reactive loop. J Biol Chem. 1995 Oct 27;270(43):25992-9. PMID:7592790