2gl9 | pdb_00002gl9

File:2gl9.gif

spinqualitylabelsall models 2gl9, resolution 2.00Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D

Crystal Structure of Glycosylasparaginase-Substrate Complex

Overview

Glycosylasparaginase (GA) plays an important role in asparagine-linked, glycoprotein degradation. A deficiency in the activity of human GA leads, to a lysosomal storage disease named aspartylglycosaminuria. GA belongs to, a superfamily of N-terminal nucleophile hydrolases that, autoproteolytically generate their mature enzymes from inactive single, chain protein precursors. The side-chain of the newly exposed N-terminal, residue then acts as a nucleophile during substrate hydrolysis. By taking, advantage of mutant enzyme of Flavobacterium meningosepticum GA with, reduced enzymatic activity, we have obtained a crystallographic snapshot, of a productive complex with its substrate (NAcGlc-Asn), at 2.0 A, resolution. This complex structure provided us an excellent model for the, Michaelis complex to examine the specific contacts critical for substrate, binding and catalysis. Substrate binding induces a conformational change, near the active site of GA. To initiate catalysis, the side-chain of the, N-terminal Thr152 is polarized by the free alpha-amino group on the same, residue, mediated by the side-chain hydroxyl group of Thr170. Cleavage of, the amide bond is then accomplished by a nucleophilic attack at the, carbonyl carbon of the amide linkage in the substrate, leading to the, formation of an acyl-enzyme intermediate through a negatively charged, tetrahedral transition state.

About this Structure

2GL9 is a Protein complex structure of sequences from Elizabethkingia meningoseptica with NAG and ASN as ligands. Active as N(4)-(beta-N-acetylglucosaminyl)-L-asparaginase, with EC number 3.5.1.26 Full crystallographic information is available from OCA.

Reference

Crystallographic snapshot of a productive glycosylasparaginase-substrate complex., Wang Y, Guo HC, J Mol Biol. 2007 Feb 9;366(1):82-92. Epub 2006 Sep 26. PMID:17157318

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