1krn | pdb_00001krn
STRUCTURE OF KRINGLE 4 AT 4C TEMPERATURE AND 1.67 ANGSTROMS RESOLUTION
Structural highlights
DiseasePLMN_HUMAN Defects in PLG are the cause of plasminogen deficiency (PLGD) [MIM:217090. PLGD is characterized by decreased serum plasminogen activity. Two forms of the disorder are distinguished: type 1 deficiency is additionally characterized by decreased plasminogen antigen levels and clinical symptoms, whereas type 2 deficiency, also known as dysplasminogenemia, is characterized by normal, or slightly reduced antigen levels, and absence of clinical manifestations. Plasminogen deficiency type 1 results in markedly impaired extracellular fibrinolysis and chronic mucosal pseudomembranous lesions due to subepithelial fibrin deposition and inflammation. The most common clinical manifestation of type 1 deficiency is ligneous conjunctivitis in which pseudomembranes formation on the palpebral surfaces of the eye progresses to white, yellow-white, or red thick masses with a wood-like consistency that replace the normal mucosa.[1] [2] [3] [4] [5] [6] [7] [8] FunctionPLMN_HUMAN Plasmin dissolves the fibrin of blood clots and acts as a proteolytic factor in a variety of other processes including embryonic development, tissue remodeling, tumor invasion, and inflammation. In ovulation, weakens the walls of the Graafian follicle. It activates the urokinase-type plasminogen activator, collagenases and several complement zymogens, such as C1 and C5. Cleavage of fibronectin and laminin leads to cell detachment and apoptosis. Also cleaves fibrin, thrombospondin and von Willebrand factor. Its role in tissue remodeling and tumor invasion may be modulated by CSPG4. Binds to cells.[9] Angiostatin is an angiogenesis inhibitor that blocks neovascularization and growth of experimental primary and metastatic tumors in vivo.[10] 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 PubMedDespite considerable effort to elucidate the functional role of the kringle domains, relatively little is known about interactions with other protein domains. Most of the crystal structures describe the interactions at the kringle active site. This study suggests a novel way to interpret structural results such as disorder located away from an active site. The crystal structure of human plasminogen kringle 4 (PGK4) has been refined against 10-1.68 A resolution X-ray data (R(merge) = 3.7%) to the standard crystallographic R = 14.7% using the program X-PLOR. The crystals of PGK4 showed significant instability in cell dimensions (changes more than 1.5 A) even at 277 K. The refinement revealed structural details not observed before [Mulichak, Tulinsky & Ravichandran (1991). Biochemistry, 30, 10576-10588], such as clear density for additional side chains and more extensive disorder. Discrete disorder was detected for residues S73, S78, T80, S89, S91, S92, Ml12, S132, C138 and K142. Most of the disordered residues form two patches on the surface of the protein. This localized disorder suggests that these residues may play a role in quaternary interactions and possibly form an interface with the other domains of proteins that contain kringles, such as plasminogen. Although, an additional residue D65 was refined at the beginning of the sequence, still more residues near the peptide cleavage site must be disordered in the crystal. Structure of human plasminogen kringle 4 at 1.68 a and 277 K. A possible structural role of disordered residues.,Stec B, Yamano A, Whitlow M, Teeter MM Acta Crystallogr D Biol Crystallogr. 1997 Mar 1;53(Pt 2):169-78. PMID:15299951[11] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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