4xwh
From Proteopedia
Crystal structure of the human N-acetyl-alpha-glucosaminidase
Structural highlights
DiseaseANAG_HUMAN Sanfilippo syndrome type B. The disease is caused by mutations affecting the gene represented in this entry. The disease is caused by mutations affecting the gene represented in this entry. FunctionANAG_HUMAN Involved in the degradation of heparan sulfate. Publication Abstract from PubMedMucopolysaccharidosis III B (MPS III-B) is a rare lysosomal storage disorder caused by deficiencies in Alpha-N-acetylglucosaminidase (NAGLU) for which there is currently no cure, and present treatment is largely supportive. Understanding the structure of NAGLU may allow for identification of novel therapeutic targets for MPS III-B. Here we describe the first crystal structure of human NAGLU, determined to a resolution of 2.3A. The crystal structure reveals a novel homotrimeric configuration, maintained primarily by hydrophobic and electrostatic interactions via domain II of three contiguous domains from the N- to C-terminus. The active site cleft is located between domains II and III. Catalytic glutamate residues, E316 and E446, are located at the top of the (alpha/beta)8 barrel structure in domain II. We utilized the three-dimensional structure of NAGLU to map several MPS III-B mutations, and hypothesize their functional consequences. Revealing atomic level structural information about this critical lysosomal enzyme paves the way for the design of novel therapeutics to target the underlying causes of MPS III-B. Structural characterization of the alpha-N-acetylglucosaminidase, a key enzyme in the pathogenesis of Sanfilippo syndrome B.,Birrane G, Dassier AL, Romashko A, Lundberg D, Holmes K, Cottle T, Norton AW, Zhang B, Concino MF, Meiyappan M J Struct Biol. 2019 Mar 1;205(3):65-71. doi: 10.1016/j.jsb.2019.02.005. Epub 2019, Feb 23. PMID:30802506[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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