1imv
From Proteopedia
2.85 A crystal structure of PEDF
Structural highlights
DiseasePEDF_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.[1] FunctionPEDF_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.[2] [3] Evolutionary ConservationCheck, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf. Publication Abstract from PubMedPigment 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[4] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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