1n2k
From Proteopedia
| Line 4: | Line 4: | ||
|PDB= 1n2k |SIZE=350|CAPTION= <scene name='initialview01'>1n2k</scene>, resolution 2.75Å | |PDB= 1n2k |SIZE=350|CAPTION= <scene name='initialview01'>1n2k</scene>, resolution 2.75Å | ||
|SITE= | |SITE= | ||
| - | |LIGAND= <scene name='pdbligand= | + | |LIGAND= <scene name='pdbligand=CA:CALCIUM+ION'>CA</scene>, <scene name='pdbligand=FGP:2-AMINO-3-HYDROXY-3-PHOSPHONOOXY-PROPIONIC+ACID'>FGP</scene>, <scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene>, <scene name='pdbligand=NDG:2-(ACETYLAMINO)-2-DEOXY-A-D-GLUCOPYRANOSE'>NDG</scene> |
| - | |ACTIVITY= [http://en.wikipedia.org/wiki/Cerebroside-sulfatase Cerebroside-sulfatase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.1.6.8 3.1.6.8] | + | |ACTIVITY= <span class='plainlinks'>[http://en.wikipedia.org/wiki/Cerebroside-sulfatase Cerebroside-sulfatase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.1.6.8 3.1.6.8] </span> |
|GENE= | |GENE= | ||
| + | |DOMAIN= | ||
| + | |RELATEDENTRY=[[1n2l|1N2L]] | ||
| + | |RESOURCES=<span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1n2k FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1n2k OCA], [http://www.ebi.ac.uk/pdbsum/1n2k PDBsum], [http://www.rcsb.org/pdb/explore.do?structureId=1n2k RCSB]</span> | ||
}} | }} | ||
| Line 14: | Line 17: | ||
==Overview== | ==Overview== | ||
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. | 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. | ||
| - | |||
| - | ==Disease== | ||
| - | Known disease associated with this structure: Metachromatic leukodystrophy OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=607574 607574]] | ||
==About this Structure== | ==About this Structure== | ||
| Line 32: | Line 32: | ||
[[Category: Monkiewicz, M.]] | [[Category: Monkiewicz, M.]] | ||
[[Category: Ortlund, E.]] | [[Category: Ortlund, E.]] | ||
| - | [[Category: CA]] | ||
| - | [[Category: NDG]] | ||
[[Category: hydrolase]] | [[Category: hydrolase]] | ||
[[Category: inhibition]] | [[Category: inhibition]] | ||
| Line 41: | Line 39: | ||
[[Category: phosphate esters hydrolysis]] | [[Category: phosphate esters hydrolysis]] | ||
| - | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sun Mar 30 22:24:29 2008'' |
Revision as of 19:24, 30 March 2008
| |||||||
| , resolution 2.75Å | |||||||
|---|---|---|---|---|---|---|---|
| Ligands: | , , , | ||||||
| Activity: | Cerebroside-sulfatase, with EC number 3.1.6.8 | ||||||
| Related: | 1N2L
| ||||||
| Resources: | FirstGlance, OCA, PDBsum, RCSB | ||||||
| Coordinates: | save as pdb, mmCIF, xml | ||||||
Crystal structure of a covalent intermediate of endogenous human arylsulfatase A
Overview
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.
About this Structure
1N2K is a Single protein structure of sequence from Homo sapiens. Full crystallographic information is available from OCA.
Reference
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
Page seeded by OCA on Sun Mar 30 22:24:29 2008
