1N2K

Crystal structure of a covalent intermediate of endogenous human arylsulfatase A

Summary for 1N2K

• Entry DOI: 10.2210/pdb1n2k/pdb
• Related: 1N2L
• Descriptor: ARYLSULFATASE A, 2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose, 2-acetamido-2-deoxy-beta-D-glucopyranose, ... (5 entities in total)
• Functional Keywords: hydrolase, phosphate esters hydrolysis, lysosomal enzyme, modified formylglycine, inhibition, metal ion
• Biological source: Homo sapiens (human)
• Total number of polymer chains: 1
• Total formula weight: 52724.42

Authors

Chruszcz, M.,Laidler, P.,Monkiewicz, M.,Ortlund, E.,Lebioda, L.,Lewinski, K. (deposition date: 2002-10-23, release date: 2003-12-23, Last modification date: 2020-07-29)

Primary citation

Chruszcz, M.,Laidler, P.,Monkiewicz, M.,Ortlund, E.,Lebioda, L.,Lewinski, K.
Crystal structure of a covalent intermediate of endogenous human arylsulfatase A.
J.Inorg.Biochem., 96:386-392, 2003

PubMed Abstract: 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.

PubMed: 12888274
DOI: 10.1016/S0162-0134(03)00176-4

Experimental method

X-RAY DIFFRACTION (2.75 Å)