1e3c
From Proteopedia
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| - | [[Image:1e3c.jpg|left|200px]] | + | [[Image:1e3c.jpg|left|200px]] |
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| - | '''CRYSTAL STRUCTURE OF AN ARYLSULFATASE A MUTANT C69S SOAKED IN SYNTHETIC SUBSTRATE''' | + | {{Structure |
| + | |PDB= 1e3c |SIZE=350|CAPTION= <scene name='initialview01'>1e3c</scene>, resolution 2.65Å | ||
| + | |SITE= | ||
| + | |LIGAND= <scene name='pdbligand=MG:MAGNESIUM ION'>MG</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] | ||
| + | |GENE= | ||
| + | }} | ||
| + | |||
| + | '''CRYSTAL STRUCTURE OF AN ARYLSULFATASE A MUTANT C69S SOAKED IN SYNTHETIC SUBSTRATE''' | ||
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==Overview== | ==Overview== | ||
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==About this Structure== | ==About this Structure== | ||
| - | 1E3C is a [ | + | 1E3C is a [[Single protein]] structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1E3C OCA]. |
==Reference== | ==Reference== | ||
| - | Crystal structure of an enzyme-substrate complex provides insight into the interaction between human arylsulfatase A and its substrates during catalysis., von Bulow R, Schmidt B, Dierks T, von Figura K, Uson I, J Mol Biol. 2001 Jan 12;305(2):269-77. PMID:[http:// | + | Crystal structure of an enzyme-substrate complex provides insight into the interaction between human arylsulfatase A and its substrates during catalysis., von Bulow R, Schmidt B, Dierks T, von Figura K, Uson I, J Mol Biol. 2001 Jan 12;305(2):269-77. PMID:[http://www.ncbi.nlm.nih.gov/pubmed/11124905 11124905] |
[[Category: Cerebroside-sulfatase]] | [[Category: Cerebroside-sulfatase]] | ||
[[Category: Homo sapiens]] | [[Category: Homo sapiens]] | ||
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[[Category: lysosomal enzyme]] | [[Category: lysosomal enzyme]] | ||
| - | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Mar 20 10:48:59 2008'' |
Revision as of 08:49, 20 March 2008
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| , resolution 2.65Å | |||||||
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| Ligands: | |||||||
| Activity: | Cerebroside-sulfatase, with EC number 3.1.6.8 | ||||||
| Coordinates: | save as pdb, mmCIF, xml | ||||||
CRYSTAL STRUCTURE OF AN ARYLSULFATASE A MUTANT C69S SOAKED IN SYNTHETIC SUBSTRATE
Contents |
Overview
Arylsulfatase A (ASA) belongs to the sulfatase family whose members carry a C(alpha)-formylglycine that is post-translationally generated by oxidation of a conserved cysteine or serine residue. The crystal structures of two arylsulfatases, ASA and ASB, and kinetic studies on ASA mutants led to different proposals for the catalytic mechanism in the hydrolysis of sulfate esters.The structures of two ASA mutants that lack the functional C(alpha)-formylglycine residue 69, in complex with a synthetic substrate, have been determined in order to unravel the reaction mechanism. The crystal structure of the inactive mutant C69A-ASA in complex with p-nitrocatechol sulfate (pNCS) mimics a reaction intermediate during sulfate ester hydrolysis by the active enzyme, without the covalent bond to the key side-chain FGly69. The structure shows that the side-chains of lysine 123, lysine 302, serine 150, histidine 229, the main-chain of the key residue 69 and the divalent cation in the active center are involved in sulfate binding. It is proposed that histidine 229 protonates the leaving alcoholate after hydrolysis.C69S-ASA is able to bind covalently to the substrate and hydrolyze it, but is unable to release the resulting sulfate. Nevertheless, the resulting sulfation is low. The structure of C69S-ASA shows the serine side-chain in a single conformation, turned away from the position a substrate occupies in the complex. This suggests that the double conformation observed in the structure of wild-type ASA is more likely to correspond to a formylglycine hydrate than to a twofold disordered aldehyde oxo group, and accounts for the relative inertness of the C69S-ASA mutant. In the C69S-ASA-pNCS complex, the substrate occupies the same position as in the C69A-ASA-pNCS complex, which corresponds to the non-covalently bonded substrate. Based on the structural data, a detailed mechanism for sulfate ester cleavage is proposed, involving an aldehyde hydrate as the functional group.
Disease
Known disease associated with this structure: Metachromatic leukodystrophy OMIM:[607574]
About this Structure
1E3C is a Single protein structure of sequence from Homo sapiens. Full crystallographic information is available from OCA.
Reference
Crystal structure of an enzyme-substrate complex provides insight into the interaction between human arylsulfatase A and its substrates during catalysis., von Bulow R, Schmidt B, Dierks T, von Figura K, Uson I, J Mol Biol. 2001 Jan 12;305(2):269-77. PMID:11124905
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