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Thesis Name: |
Structural Insights into the Catalytic Mechanism of Phosphate Ester Hydrolysis by dUTPase |
Usage: |
Biochemitry |
Keyword: |
Structural Insights into the Catalytic Mechanism of Phosphate Ester Hydrolysis by dUTPase |
Remarks: |
dUTPase is essential to keep uracil out of DNA. Crystal structures of substrate (dUTP and ,-imino-dUTP) and product complexes of wild type and mutant dUTPases were determined to reveal how an enzyme responsible for DNA integrity functions. A kinetic analysis of wild type and mutant dUTPases was performed to obtain relevant mechanistic information in solution. Substrate hydrolysis is shown to be initiated via in-line nucleophile attack of a water molecule oriented by an activating conserved aspartate residue. Substrate binding in a catalytically competent conformation is achieved by (i) multiple interactions of the triphosphate moiety with catalysis-assisting Mg2+, (ii) a concerted motion of residues from three conserved enzyme motifs as compared with the apoenzyme, and (iii) an intricate hydrogen-bonding network that includes several water molecules in the active site. Results provide an understanding for the catalytic role of conserved residues in dUTPases. |
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Promulgator Detail |
Full name: |
hichem |
Country: |
CN |
City: |
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Company Name: |
hichem |
Homepage: |
http://www.teloon.com |
E-mail: |
reply |
Phone: |
86-411-82819585 |
Fax: |
86-411-82819612 |
Company Address: |
Renming Road, Dalian city, Lianning pro,china |
Zip/Postal Code: |
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