3b9x

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{{STRUCTURE_3b9x| PDB=3b9x | SCENE= }}
{{STRUCTURE_3b9x| PDB=3b9x | SCENE= }}
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'''Crystal structure of the E. coli pyrimidine nucleoside hydrolase YeiK in complex with inosine'''
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===Crystal structure of the E. coli pyrimidine nucleoside hydrolase YeiK in complex with inosine===
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==Overview==
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Enzymes with nucleoside hydrolase activity (NHs) belonging to homology group I either are markedly specific for pyrimidine nucleoside substrates or hydrolyze with comparable efficiencies the N-glycosidic bond in all common nucleosides. The biochemical and structural basis for these differences in substrate specificity is still unknown. Here we characterize the binding interactions between the slowly hydrolyzed substrate inosine and the Escherichia coli pyrimidine-specific NH YeiK using cryotrapping and X-ray crystallography. Guided by the structural features of the Michaelis complex, we show the synergic effect of two specific point mutations in YeiK that increase the catalytic efficiency toward purine nucleosides to values comparable to those of natural nonspecific NHs. We demonstrate that the integrity of an active-site catalytic triad comprised of two hydroxylated amino acids and one histidine residue is a requirement for the highly efficient hydrolysis of inosine by group I NHs. Instead, cleavage of the YeiK-preferred substrate uridine is not affected by mutations at the same locations, suggesting a different fine chemical mechanism for the hydrolysis of the two nucleoside substrates. Our study provides for the first time direct evidence that distinct subsets of amino acid residues are involved in the hydrolysis of purine or pyrimidine nucleosides in group I NHs.
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The line below this paragraph, {{ABSTRACT_PUBMED_18361502}}, adds the Publication Abstract to the page
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(as it appears on PubMed at http://www.pubmed.gov), where 18361502 is the PubMed ID number.
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{{ABSTRACT_PUBMED_18361502}}
==About this Structure==
==About this Structure==
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==Reference==
==Reference==
Structural Basis for Substrate Specificity in Group I Nucleoside Hydrolases(,)., Iovane E, Giabbai B, Muzzolini L, Matafora V, Fornili A, Minici C, Giannese F, Degano M, Biochemistry. 2008 Mar 25;. PMID:[http://www.ncbi.nlm.nih.gov/pubmed/18361502 18361502]
Structural Basis for Substrate Specificity in Group I Nucleoside Hydrolases(,)., Iovane E, Giabbai B, Muzzolini L, Matafora V, Fornili A, Minici C, Giannese F, Degano M, Biochemistry. 2008 Mar 25;. PMID:[http://www.ncbi.nlm.nih.gov/pubmed/18361502 18361502]
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Crystal structure to 1.7 a of the Escherichia coli pyrimidine nucleoside hydrolase YeiK, a novel candidate for cancer gene therapy., Giabbai B, Degano M, Structure. 2004 May;12(5):739-49. PMID:[http://www.ncbi.nlm.nih.gov/pubmed/15130467 15130467]
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Trypanosomal nucleoside hydrolase. A novel mechanism from the structure with a transition-state inhibitor., Degano M, Almo SC, Sacchettini JC, Schramm VL, Biochemistry. 1998 May 5;37(18):6277-85. PMID:[http://www.ncbi.nlm.nih.gov/pubmed/9572842 9572842]
[[Category: Escherichia coli]]
[[Category: Escherichia coli]]
[[Category: Ribosylpyrimidine nucleosidase]]
[[Category: Ribosylpyrimidine nucleosidase]]
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[[Category: Nh-fold]]
[[Category: Nh-fold]]
[[Category: Protein-nucleoside complex]]
[[Category: Protein-nucleoside complex]]
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Apr 24 09:32:23 2008''
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Tue Jul 29 08:25:49 2008''

Revision as of 05:25, 29 July 2008

Template:STRUCTURE 3b9x

Crystal structure of the E. coli pyrimidine nucleoside hydrolase YeiK in complex with inosine

Template:ABSTRACT PUBMED 18361502

About this Structure

3B9X is a Single protein structure of sequence from Escherichia coli. Full crystallographic information is available from OCA.

Reference

Structural Basis for Substrate Specificity in Group I Nucleoside Hydrolases(,)., Iovane E, Giabbai B, Muzzolini L, Matafora V, Fornili A, Minici C, Giannese F, Degano M, Biochemistry. 2008 Mar 25;. PMID:18361502

Crystal structure to 1.7 a of the Escherichia coli pyrimidine nucleoside hydrolase YeiK, a novel candidate for cancer gene therapy., Giabbai B, Degano M, Structure. 2004 May;12(5):739-49. PMID:15130467

Trypanosomal nucleoside hydrolase. A novel mechanism from the structure with a transition-state inhibitor., Degano M, Almo SC, Sacchettini JC, Schramm VL, Biochemistry. 1998 May 5;37(18):6277-85. PMID:9572842

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