2gl9

From Proteopedia

(Difference between revisions)
Jump to: navigation, search
(New page: 200px<br /><applet load="2gl9" size="450" color="white" frame="true" align="right" spinBox="true" caption="2gl9, resolution 2.00&Aring;" /> '''Crystal Structure of...)
Line 1: Line 1:
-
[[Image:2gl9.gif|left|200px]]<br /><applet load="2gl9" size="450" color="white" frame="true" align="right" spinBox="true"
+
[[Image:2gl9.gif|left|200px]]<br /><applet load="2gl9" size="350" color="white" frame="true" align="right" spinBox="true"
caption="2gl9, resolution 2.00&Aring;" />
caption="2gl9, resolution 2.00&Aring;" />
'''Crystal Structure of Glycosylasparaginase-Substrate Complex'''<br />
'''Crystal Structure of Glycosylasparaginase-Substrate Complex'''<br />
==Overview==
==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.
+
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==
==About this Structure==
-
2GL9 is a [http://en.wikipedia.org/wiki/Protein_complex Protein complex] structure of sequences from [http://en.wikipedia.org/wiki/Elizabethkingia_meningoseptica Elizabethkingia meningoseptica] with NAG and ASN as [http://en.wikipedia.org/wiki/ligands ligands]. Active as [http://en.wikipedia.org/wiki/N(4)-(beta-N-acetylglucosaminyl)-L-asparaginase N(4)-(beta-N-acetylglucosaminyl)-L-asparaginase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.5.1.26 3.5.1.26] Full crystallographic information is available from [http://ispc.weizmann.ac.il/oca-bin/ocashort?id=2GL9 OCA].
+
2GL9 is a [http://en.wikipedia.org/wiki/Protein_complex Protein complex] structure of sequences from [http://en.wikipedia.org/wiki/Elizabethkingia_meningoseptica Elizabethkingia meningoseptica] with <scene name='pdbligand=NAG:'>NAG</scene> and <scene name='pdbligand=ASN:'>ASN</scene> as [http://en.wikipedia.org/wiki/ligands ligands]. Active as [http://en.wikipedia.org/wiki/N(4)-(beta-N-acetylglucosaminyl)-L-asparaginase N(4)-(beta-N-acetylglucosaminyl)-L-asparaginase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.5.1.26 3.5.1.26] Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2GL9 OCA].
==Reference==
==Reference==
Line 14: Line 14:
[[Category: N(4)-(beta-N-acetylglucosaminyl)-L-asparaginase]]
[[Category: N(4)-(beta-N-acetylglucosaminyl)-L-asparaginase]]
[[Category: Protein complex]]
[[Category: Protein complex]]
-
[[Category: Guo, H.C.]]
+
[[Category: Guo, H C.]]
[[Category: Wang, Y.]]
[[Category: Wang, Y.]]
[[Category: ASN]]
[[Category: ASN]]
Line 29: Line 29:
[[Category: proton-relay network]]
[[Category: proton-relay network]]
-
''Page seeded by [http://ispc.weizmann.ac.il/oca OCA ] on Wed Nov 21 11:15:26 2007''
+
''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 17:32:45 2008''

Revision as of 15:32, 21 February 2008

Image:2gl9.gif

2gl9, resolution 2.00Å

Drag the structure with the mouse to rotate

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 and 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

Page seeded by OCA on Thu Feb 21 17:32:45 2008

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/2gl9"
Personal tools