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Title: Comprehensive X-Ray Structural Studies of the Quinolinate Phosphoribosyl Transferase (BNA6) From Saccharomyces Cerevisiae

Abstract

Quinolinic acid phosphoribosyl transferase (QAPRTase, EC 2.4.2.19) is a 32 kDa enzyme encoded by the BNA6 gene in yeast and catalyzes the formation of nicotinate mononucleotide from quinolinate and 5-phosphoribosyl-1-pyrophosphate (PRPP). QAPRTase plays a key role in the tryptophan degradation pathway via kynurenine, leading to the de novo biosynthesis of NAD{sup +} and clearing the neurotoxin quinolinate. To improve our understanding of the specificity of the eukaryotic enzyme and the course of events associated with catalysis, we have determined the crystal structures of the apo and singly bound forms with the substrates quinolinate and PRPP. This reveals that the enzyme folds in a manner similar to that of various prokaryotic forms which are {approx}30% identical in sequence. In addition, the structure of the Michaelis complex is approximated by PRPP and the quinolinate analogue phthalate bound to the active site. These results allow insight into the kinetic mechanism of QAPRTase and provide an understanding of structural diversity in the active site of the Saccharomyces cerevisiae enzyme when compared to prokaryotic homologues.

Authors:
;
Publication Date:
Research Org.:
SLAC National Accelerator Lab., Menlo Park, CA (United States)
Sponsoring Org.:
USDOE
OSTI Identifier:
958588
Report Number(s):
SLAC-REPRINT-2009-105
Journal ID: ISSN 0006-2960; BICHAW; TRN: US201001%%748
DOE Contract Number:  
AC02-76SF00515
Resource Type:
Journal Article
Journal Name:
Biochem.47:4039,2008
Additional Journal Information:
Journal Volume: 47; Journal Issue: 13; Journal ID: ISSN 0006-2960
Country of Publication:
United States
Language:
English
Subject:
36 MATERIALS SCIENCE; BIOSYNTHESIS; CATALYSIS; CRYSTAL STRUCTURE; ENZYMES; GENES; KINETICS; KYNURENINE; PHTHALATES; SACCHAROMYCES CEREVISIAE; SPECIFICITY; SUBSTRATES; TRANSFERASES; TRYPTOPHAN; YEASTS; Other,BIO, CHEM

Citation Formats

di Luccio, E, and Wilson, D K. Comprehensive X-Ray Structural Studies of the Quinolinate Phosphoribosyl Transferase (BNA6) From Saccharomyces Cerevisiae. United States: N. p., 2009. Web.
di Luccio, E, & Wilson, D K. Comprehensive X-Ray Structural Studies of the Quinolinate Phosphoribosyl Transferase (BNA6) From Saccharomyces Cerevisiae. United States.
di Luccio, E, and Wilson, D K. 2009. "Comprehensive X-Ray Structural Studies of the Quinolinate Phosphoribosyl Transferase (BNA6) From Saccharomyces Cerevisiae". United States.
@article{osti_958588,
title = {Comprehensive X-Ray Structural Studies of the Quinolinate Phosphoribosyl Transferase (BNA6) From Saccharomyces Cerevisiae},
author = {di Luccio, E and Wilson, D K},
abstractNote = {Quinolinic acid phosphoribosyl transferase (QAPRTase, EC 2.4.2.19) is a 32 kDa enzyme encoded by the BNA6 gene in yeast and catalyzes the formation of nicotinate mononucleotide from quinolinate and 5-phosphoribosyl-1-pyrophosphate (PRPP). QAPRTase plays a key role in the tryptophan degradation pathway via kynurenine, leading to the de novo biosynthesis of NAD{sup +} and clearing the neurotoxin quinolinate. To improve our understanding of the specificity of the eukaryotic enzyme and the course of events associated with catalysis, we have determined the crystal structures of the apo and singly bound forms with the substrates quinolinate and PRPP. This reveals that the enzyme folds in a manner similar to that of various prokaryotic forms which are {approx}30% identical in sequence. In addition, the structure of the Michaelis complex is approximated by PRPP and the quinolinate analogue phthalate bound to the active site. These results allow insight into the kinetic mechanism of QAPRTase and provide an understanding of structural diversity in the active site of the Saccharomyces cerevisiae enzyme when compared to prokaryotic homologues.},
doi = {},
url = {https://www.osti.gov/biblio/958588}, journal = {Biochem.47:4039,2008},
issn = {0006-2960},
number = 13,
volume = 47,
place = {United States},
year = {Thu May 14 00:00:00 EDT 2009},
month = {Thu May 14 00:00:00 EDT 2009}
}