1n2k
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Crystal structure of a covalent intermediate of endogenous human arylsulfatase A
OverviewOverview
The structures of human arylsulfatase A crystals soaked in solutions, containing 4-methylumbelliferyl phosphate and O-phospho-DL-tyrosine have, been determined at 2.7- and 3.2-A resolution, respectively. The, formylglycine in position 69, a residue crucial for catalytic activity, was unambiguously identified in both structures as forming a covalent bond, to the phosphate moiety. A hydroxyl group is present at the Cbeta of, residue 69 and the formation of one out of two possible stereomeric forms, is strongly favoured. The structures confirm the importance of the, gem-diol intermediate in the arylsulfatase's catalytic mechanism. The, presence of an apparently stable covalent bond is consistent with the weak, phosphatase activity observed for human arylsulfatase A. The structures of, the complexes suggest that phosphate ions and phosphate esters inhibit, arylsulfatase in non-covalent and covalent modes, respectively. The metal, ion present in the active site of arylsulfatase A isolated from human, placenta is Ca(2+) and not Mg(2+) as was found in the structure of the, recombinant enzyme.
DiseaseDisease
Known disease associated with this structure: Metachromatic leukodystrophy OMIM:[607574]
About this StructureAbout this Structure
1N2K is a Single protein structure of sequence from Homo sapiens with NDG and CA as ligands. Active as Cerebroside-sulfatase, with EC number 3.1.6.8 Full crystallographic information is available from OCA.
ReferenceReference
Crystal structure of a covalent intermediate of endogenous human arylsulfatase A., Chruszcz M, Laidler P, Monkiewicz M, Ortlund E, Lebioda L, Lewinski K, J Inorg Biochem. 2003 Aug 1;96(2-3):386-92. PMID:12888274
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