3ohg
From Proteopedia
Crystal structure of a protein with unknown function from DUF2233 family (BACOVA_00430) from Bacteroides ovatus at 1.80 A resolution
Structural highlights
FunctionEvolutionary ConservationCheck, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf. Publication Abstract from PubMedDUF2233, a domain of unknown function (DUF), is present in many bacterial and several viral proteins and was also identified in the mammalian transmembrane glycoprotein N-acetylglucosamine-1-phosphodiester alpha-N-acetylglucosaminidase ("uncovering enzyme" (UCE)). We report the crystal structure of BACOVA_00430, a 315-residue protein from the human gut bacterium Bacteroides ovatus that is the first structural representative of the DUF2233 protein family. A notable feature of this structure is the presence of a surface cavity that is populated by residues that are highly conserved across the entire family. The crystal structure was used to model the luminal portion of human UCE (hUCE), which is involved in targeting of lysosomal enzymes. Mutational analysis of several residues in a highly conserved surface cavity of hUCE revealed that they are essential for function. The bacterial enzyme (BACOVA_00430) has approximately 1% of the catalytic activity of hUCE toward the substrate GlcNAc-P-mannose, the precursor of the Man-6-P lysosomal targeting signal. GlcNAc-1-P is a poor substrate for both enzymes. We conclude that, for at least a subset of proteins in this family, DUF2233 functions as a phosphodiester glycosidase. Structure and function of the DUF2233 domain in bacteria and in the human mannose 6-phosphate uncovering enzyme.,Das D, Lee WS, Grant JC, Chiu HJ, Farr CL, Vance J, Klock HE, Knuth MW, Miller MD, Elsliger MA, Deacon AM, Godzik A, Lesley SA, Kornfeld S, Wilson IA J Biol Chem. 2013 Jun 7;288(23):16789-99. doi: 10.1074/jbc.M112.434977. Epub 2013, Apr 9. PMID:23572527[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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