3edg
From Proteopedia
Crystal structure of bone morphogenetic protein 1 protease domain
Structural highlights
DiseaseBMP1_HUMAN Defects in BMP1 are the cause of osteogenesis imperfecta 13 (OI13) [MIM:614856. An autosomal recessive form of osteogenesis imperfecta, a connective tissue disorder characterized by bone fragility, low bone mass, and recurrent fractures. OI13 is characterized by normal teeth, faint blue sclerae, severe growth deficiency, borderline osteoporosis, severe bone deformity, and recurrent fractures affecting both upper and lower limbs.[1] [2] FunctionBMP1_HUMAN Cleaves the C-terminal propeptides of procollagen I, II and III. Induces cartilage and bone formation. May participate in dorsoventral patterning during early development by cleaving chordin (CHRD). Responsible for the proteolytic activation of lysyl oxidase LOX. Evolutionary Conservation Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf. Publication Abstract from PubMedProcollagen C-peptidase, also known as bone morphogenetic protein 1 (BMP-1), is a multidomain, zinc endopeptidase of the astacin M12A family. BMP-1 is the prototype of a small group of proteases that have key roles in extracellular matrix formation and morphogenesis. BMP-1, its splice form mTLD, and the related proteases TLL-1 and TLL-2 are considered as promising drug targets for the treatment of excessive fibrosis and muscle wasting. We report here the crystal structures of the protease domains of human BMP-1 and the closely related Tolloid-like protease 1 (TLL-1). The crystal structures reveal an unexpected conformation of a cysteine-rich loop within the active site, and suggest that a flap movement is required in order to allow substrate binding. On the basis of these substantial differences between the BMP-1 and astacin active sites, a structural basis for their differing substrate specificities is proposed. Structural basis for the substrate specificity of bone morphogenetic protein 1/tolloid-like metalloproteases.,Mac Sweeney A, Gil-Parrado S, Vinzenz D, Bernardi A, Hein A, Bodendorf U, Erbel P, Logel C, Gerhartz B J Mol Biol. 2008 Dec 5;384(1):228-39. doi: 10.1016/j.jmb.2008.09.029. Epub 2008 , Sep 19. PMID:18824173[3] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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