Details:

Alternative Title:
BMC Res Notes
Publisher's site:
http://dx.doi.org/10.1186/s13104-015-1760-1
Personal Author:
Inoguchi, Noriko ; Chaiseeda, Kittichai ; Yamanishi, Mamoru ; Kim, Moon Ki ; Jang, Yunho ; ... More +
Inoguchi, Noriko ; Chaiseeda, Kittichai ; Yamanishi, Mamoru ; Kim, Moon Ki ; Jang, Yunho ; Bajaj, Mamta ; Chia, Catherine P. ; Becker, Donald F. ; Moriyama, Hideaki ; Less -
Description:
Background Deoxyuridine triphosphate nucleotidohydrolase (dUTPase) hydrolyzes dUTP to dUMP and pyrophosphate to maintain the cellular thymine-uracil ratio. dUTPase is also a target for cancer chemotherapy. However, the mechanism defining its substrate affinity remains unclear. Sequence comparisons of various dUTPases revealed that Arabidopsis thaliana dUTPase has a unique tryptophan at position 93, which potentially contributes to its degree of substrate affinity. To better understand the roles of tryptophan 93, A. thaliana dUTPase was studied. Results Enzyme assays showed that A. thaliana dUTPase belongs to a high-affinity group of isozymes, which also includes the enzymes from Escherichia coli and Mycobacterium tuberculosis. Enzymes from Homo sapiens and Saccharomyces cerevisiae are grouped as low-affinity dUTPases. The structure of the homo-trimeric A. thaliana dUTPase showed three active sites, each with a different set of ligand interactions between the amino acids and water molecules. On an α-helix, tryptophan 93 appears to keep serine 89 in place via a water molecule and to specifically direct the ligand. Upon being oriented in the active site, the C-terminal residues close the active site to promote the reaction. Conclusions In the high-affinity group, the prefixed direction of the serine residues was oriented by a positively charged residue located four amino acids away, while low-affinity enzymes possess small hydrophobic residues at the corresponding sites. Electronic supplementary material The online version of this article (doi:10.1186/s13104-015-1760-1) contains supplementary material, which is available to authorized users.
Subject:
[+]
Arabidopsis Thaliana
Deoxyuridine Triphosphate Nucleotidohydrolase
Drug Targets
Research Article
Substrate Affinity

Source:
BMC Res Notes. 8. ;
Pubmed ID:
26666293
Pubmed Central ID:
PMC4678481
Document Type:
Journal Article ;
Collection(s):
CDC Public Access
Main Document Checksum:
[+]
urn:sha256:00dbda34c940988600cd814cc81f25522022661958bebf428f6dd87beafee738
File Type:

Supporting Files

• 	13104_2015_1760_MOESM1_ESM.docx	docx
  	13104_2015_1760_MOESM2_ESM.docx	docx
  	13104_2015_1760_MOESM3_ESM.docx	docx
  	13104_2015_Article_1760.nxml	bin
  	license.txt	txt
  	13104_2015_1760_Fig1_HTML.gif	gif
  	13104_2015_1760_Fig1_HTML.jpg	jpeg
  	13104_2015_1760_Fig2_HTML.gif	gif
  	13104_2015_1760_Fig2_HTML.jpg	jpeg
  	13104_2015_1760_Fig3_HTML.gif	gif
  	13104_2015_1760_Fig3_HTML.jpg	jpeg

More +