7s4y
From Proteopedia
Serial Macromolecular Crystallography at ALBA Synchrotron Light Source - Insulin
Structural highlights
DiseaseINS_HUMAN Defects in INS are the cause of familial hyperproinsulinemia (FHPRI) [MIM:176730.[1] [2] [3] [4] Defects in INS are a cause of diabetes mellitus insulin-dependent type 2 (IDDM2) [MIM:125852. IDDM2 is a multifactorial disorder of glucose homeostasis that is characterized by susceptibility to ketoacidosis in the absence of insulin therapy. Clinical fetaures are polydipsia, polyphagia and polyuria which result from hyperglycemia-induced osmotic diuresis and secondary thirst. These derangements result in long-term complications that affect the eyes, kidneys, nerves, and blood vessels.[5] Defects in INS are a cause of diabetes mellitus permanent neonatal (PNDM) [MIM:606176. PNDM is a rare form of diabetes distinct from childhood-onset autoimmune diabetes mellitus type 1. It is characterized by insulin-requiring hyperglycemia that is diagnosed within the first months of life. Permanent neonatal diabetes requires lifelong therapy.[6] [7] Defects in INS are a cause of maturity-onset diabetes of the young type 10 (MODY10) [MIM:613370. MODY10 is a form of diabetes that is characterized by an autosomal dominant mode of inheritance, onset in childhood or early adulthood (usually before 25 years of age), a primary defect in insulin secretion and frequent insulin-independence at the beginning of the disease.[8] [9] [10] FunctionINS_HUMAN Insulin decreases blood glucose concentration. It increases cell permeability to monosaccharides, amino acids and fatty acids. It accelerates glycolysis, the pentose phosphate cycle, and glycogen synthesis in liver. Publication Abstract from PubMedThe increase in successful adaptations of serial crystallography at synchrotron radiation sources continues. To date, the number of serial synchrotron crystallography (SSX) experiments has grown exponentially, with over 40 experiments reported so far. In this work, we report the first SSX experiments with viscous jets conducted at ALBA beamline BL13-XALOC. Small crystals (15-30 microm) of five soluble proteins (lysozyme, proteinase K, phycocyanin, insulin and alpha-spectrin-SH3 domain) were suspended in lipidic cubic phase (LCP) and delivered to the X-ray beam with a high-viscosity injector developed at Arizona State University. Complete data sets were collected from all proteins and their high-resolution structures determined. The high quality of the diffraction data collected from all five samples, and the lack of specific radiation damage in the structures obtained in this study, confirm that the current capabilities at the beamline enables atomic resolution determination of protein structures from microcrystals as small as 15 microm using viscous jets at room temperature. Thus, BL13-XALOC can provide a feasible alternative to X-ray free-electron lasers when determining snapshots of macromolecular structures. Serial macromolecular crystallography at ALBA Synchrotron Light Source.,Martin-Garcia JM, Botha S, Hu H, Jernigan R, Castellvi A, Lisova S, Gil F, Calisto B, Crespo I, Roy-Chowdhury S, Grieco A, Ketawala G, Weierstall U, Spence J, Fromme P, Zatsepin N, Boer DR, Carpena X J Synchrotron Radiat. 2022 May 1;29(Pt 3):896-907. doi:, 10.1107/S1600577522002508. Epub 2022 Apr 4. PMID:35511023[11] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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Categories: Homo sapiens | Large Structures | Boer R | Botha S | Calisto B | Carpena X | Castellvi A | Crespo I | Fromme P | Gil F | Grieco A | Hu H | Jernigan R | Ketawala G | Lisova S | Martin-Garcia JM | Roy-Chowdbury S | Spence J | Weierstall U | Zatsepin N