Online citations, reference lists, and bibliographies.
Please confirm you are human
(Sign Up for free to never see this)
← Back to Search

New Insights Into The Mechanism Of Nucleoside Hydrolases From The Crystal Structure Of The Escherichia Coli YbeK Protein Bound To The Reaction Product.

Laura Muzzolini, W. Versées, P. Tornaghi, Els Van Holsbeke, J. Steyaert, M. Degano
Published 2006 · Chemistry, Medicine

Save to my Library
Download PDF
Analyze on Scholarcy
Share
Nucleoside hydrolases (NHs) are enzymes that catalyze the excision of the N-glycosidic bond in nucleosides to allow recycling of the nitrogenous bases. The fine details of the catalytic mechanism and the structural features imposing the substrate specificity of the various members of the NH family are still debated. Here we present the functional characterization of the Escherichia coli YbeK (RihA) protein as a pyrimidine nucleoside-preferring NH and its first crystal structure to 1.8 A resolution. The enzyme active site is occupied by either the alpha or beta anomer of ribose and provides the first structural description of the binding of the NH reaction product. While the amino acid residues involved in ribosyl binding are strictly conserved in pyrimidine-specific NHs, the residues involved in specific interactions with the nitrogenous bases differ considerably. Further comparison of the active site architecture of YbeK with the related NHs establishes structural determinants involved in triggering the conformational transition between the open and closed structures and suggests a mechanism for product release.



This paper is referenced by
10.1002/pro.3141
Structural and biochemical characterization of the nucleoside hydrolase from C. elegans reveals the role of two active site cysteine residues in catalysis
R. Singh (2017)
Structure and Function of Nucleoside Hydrolases from Physcomitrella patens and Maize Catalyzing the Hydrolysis of Purine , Pyrimidine , and Cytokinin Ribosides 1 [ W ]
M. Kope (2013)
10.1007/s13213-011-0379-2
Site-directed mutagenesis gives insights into substrate specificity of Sulfolobus solfataricus purine-specific nucleoside hydrolase
M. Porcelli (2011)
10.1186/1472-6807-10-14
Active site plasticity revealed from the structure of the enterobacterial N-ribohydrolase RihA bound to a competitive inhibitor
G. Garau (2009)
10.1021/jp211403j
QM/MM molecular dynamics study of purine-specific nucleoside hydrolase.
Ruibo Wu (2012)
10.1128/AAC.01787-09
Evaluation of Nucleoside Hydrolase Inhibitors for Treatment of African Trypanosomiasis
M. Berg (2010)
10.1016/j.cbi.2016.12.004
The importance of nucleoside hydrolase enzyme (NH) in studies to treatment of Leishmania: A review.
J. D. Figueroa-Villar (2017)
KINETIC MECHANISM OF NUCLEOSIDE HYDROLASE FROM ESCHERICHIA
M. Farone (2016)
10.1016/j.abb.2008.12.005
Biochemical characterization and homology modeling of a purine-specific ribonucleoside hydrolase from the archaeon Sulfolobus solfataricus: insights into mechanisms of protein stabilization.
M. Porcelli (2009)
10.1021/bi702448s
Structural basis for substrate specificity in group I nucleoside hydrolases.
E. Iovane (2008)
10.1128/ecosalplus.3.6.2
Nucleotides, Nucleosides, and Nucleobases.
K. Jensen (2008)
10.1021/BI300209G
New determinants in the catalytic mechanism of nucleoside hydrolases from the structures of two isozymes from Sulfolobus solfataricus.
C. Minici (2012)
10.1139/V09-024
Glycosidic bond cleavage in deoxynucleotides — A density functional study
Andrea L. Millen (2009)
10.1002/cmdc.200800231
Synthesis of Bicyclic N‐Arylmethyl‐Substituted Iminoribitol Derivatives as Selective Nucleoside Hydrolase Inhibitors
M. Berg (2009)
10.1002/pro.3812
Solution structure of the nucleotide hydrolase BlsM: Implication of its substrate specificity
Minhee Kang (2019)
10.1111/j.1742-4658.2008.06348.x
Pyrimidine‐specific ribonucleoside hydrolase from the archaeon Sulfolobus solfataricus– biochemical characterization and homology modeling
M. Porcelli (2008)
10.1104/pp.113.228775
Structure and Function of Nucleoside Hydrolases from Physcomitrella patens and Maize Catalyzing the Hydrolysis of Purine, Pyrimidine, and Cytokinin Ribosides1[W]
Martina Kopečná (2013)
10.1016/j.bbapap.2014.01.010
Characterization of inosine-uridine nucleoside hydrolase (RihC) from Escherichia coli.
Brock A Arivett (2014)
10.1016/j.bmc.2008.05.056
N-Arylmethyl substituted iminoribitol derivatives as inhibitors of a purine specific nucleoside hydrolase.
A. Goeminne (2008)
10.1080/07391102.2012.674293
Molecular modeling studies on nucleoside hydrolase from the biological warfare agent Brucella suis
D. T. Mancini (2012)
Semantic Scholar Logo Some data provided by SemanticScholar