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Title: Functional Annotation and Structural Characterization of a Novel Lactonase Hydrolyzing d-Xylono-1,4-lactone-5-phosphate and l-Arabino-1,4-lactone-5-phosphate

Authors:
; ; ; ; ; ; ; ; ;
Publication Date:
Research Org.:
Brookhaven National Laboratory (BNL)
Sponsoring Org.:
USDOE SC OFFICE OF SCIENCE (SC)
OSTI Identifier:
1162627
Report Number(s):
BNL-106572-2014-JA
Journal ID: ISSN 0006--2960
DOE Contract Number:
DE-AC02-98CH10886
Resource Type:
Journal Article
Resource Relation:
Journal Name: Biochemistry; Journal Volume: 53; Journal Issue: 28
Country of Publication:
United States
Language:
English

Citation Formats

Korczynska, M., Xiang, D., Zhang, Z., Xu, C., Narindoshvili, T., Kamat, S., Williams, H., Chang, S., Kolb, P., and et al. Functional Annotation and Structural Characterization of a Novel Lactonase Hydrolyzing d-Xylono-1,4-lactone-5-phosphate and l-Arabino-1,4-lactone-5-phosphate. United States: N. p., 2014. Web. doi:10.1021/bi500595c.
Korczynska, M., Xiang, D., Zhang, Z., Xu, C., Narindoshvili, T., Kamat, S., Williams, H., Chang, S., Kolb, P., & et al. Functional Annotation and Structural Characterization of a Novel Lactonase Hydrolyzing d-Xylono-1,4-lactone-5-phosphate and l-Arabino-1,4-lactone-5-phosphate. United States. doi:10.1021/bi500595c.
Korczynska, M., Xiang, D., Zhang, Z., Xu, C., Narindoshvili, T., Kamat, S., Williams, H., Chang, S., Kolb, P., and et al. Tue . "Functional Annotation and Structural Characterization of a Novel Lactonase Hydrolyzing d-Xylono-1,4-lactone-5-phosphate and l-Arabino-1,4-lactone-5-phosphate". United States. doi:10.1021/bi500595c.
@article{osti_1162627,
title = {Functional Annotation and Structural Characterization of a Novel Lactonase Hydrolyzing d-Xylono-1,4-lactone-5-phosphate and l-Arabino-1,4-lactone-5-phosphate},
author = {Korczynska, M. and Xiang, D. and Zhang, Z. and Xu, C. and Narindoshvili, T. and Kamat, S. and Williams, H. and Chang, S. and Kolb, P. and et al.},
abstractNote = {},
doi = {10.1021/bi500595c},
journal = {Biochemistry},
number = 28,
volume = 53,
place = {United States},
year = {Tue Jul 22 00:00:00 EDT 2014},
month = {Tue Jul 22 00:00:00 EDT 2014}
}
  • 3-Deoxy-D-arabino-heptulosonate 7-phosphate synthase (DAHPS) catalyzes the first step in the biosynthesis of a number of aromatic metabolites. Likely because this reaction is situated at a pivotal biosynthetic gateway, several DAHPS classes distinguished by distinct mechanisms of allosteric regulation have independently evolved. One class of DAHPSs contains a regulatory domain with sequence homology to chorismate mutase - an enzyme further downstream of DAHPS that catalyzes the first committed step in tyrosine/phenylalanine biosynthesis - and is inhibited by chorismate mutase substrate (chorismate) and product (prephenate). Described in this work, structures of the Listeria monocytogenes chorismate/prephenate regulated DAHPS in complex with Mn{sup 2+}more » and Mn{sup 2+} + phosphoenolpyruvate reveal an unusual quaternary architecture: DAHPS domains assemble as a tetramer, from either side of which chorismate mutase-like (CML) regulatory domains asymmetrically emerge to form a pair of dimers. This domain organization suggests that chorismate/prephenate binding promotes a stable interaction between the discrete regulatory and catalytic domains and supports a mechanism of allosteric inhibition similar to tyrosine/phenylalanine control of a related DAHPS class. We argue that the structural similarity of chorismate mutase enzyme and CML regulatory domain provides a unique opportunity for the design of a multitarget antibacterial.« less
  • The 'ribulose phosphate binding' superfamily defined by the Structural Classification of Proteins (SCOP) database is considered the result of divergent evolution from a common ({beta}/{alpha}){sub 8}-barrel ancestor. The superfamily includes D-ribulose 5-phosphate 3-epimerase (RPE), orotidine 5'-monophosphate decarboxylase (OMPDC), and 3-keto-L-gulonate 6-phosphate decarboxylase (KGPDC), members of the OMPDC suprafamily, as well as enzymes involved in histidine and tryptophan biosynthesis that utilize phosphorylated metabolites as substrates. We now report studies of the functional and structural relationships of RPE to the members of the superfamily. As suggested by the results of crystallographic studies of the RPEs from rice and Plasmodium falciparum, the RPEmore » from Streptococcus pyogenes is activated by Zn{sup 2+} which binds with a stoichiometry of one ion per polypeptide. Although wild type RPE has a high affinity for Zn{sup 2+} and inactive apoenzyme cannot be prepared, the affinity for Zn{sup 2+} is decreased by alanine substitutions for the two histidine residues that coordinate the Zn{sup 2+} ion (H34A and H67A); these mutant proteins can be prepared in an inactive, metal-free form and activated by exogenous Zn{sup 2+}. The crystal structure of the RPE was solved at 1.8 Angstroms resolution in the presence of D-xylitol 5-phosphate, an inert analogue of the D-xylulose 5-phosphate substrate. This structure suggests that the 2,3-enediolate intermediate in the 1,1-proton transfer reaction is stabilized by bidentate coordination to the Zn{sup 2+} that also is liganded to His 34, Asp 36, His 67, and Asp 176; the carboxylate groups of the Asp residues are positioned also to function as the acid/base catalysts. Although the conformation of the bound analogue resembles those of ligands bound in the active sites of OMPDC and KGPDC, the identities of the active site residues that coordinate the essential Zn{sup 2+} and participate as acid/base catalysts are not conserved. We conclude that only the phosphate binding motif located at the ends of the seventh and eighth {beta}-strands of the ({beta}/{alpha}){sub 8}-barrel is functionally conserved among RPE, OMPDC, and KGPDC, consistent with the hypothesis that the members of the 'ribulose phosphate binding' ({beta}/{alpha}){sub 8}-barrel 'superfamily' as defined by SCOP have not evolved by evolutionary processes involving the intact ({beta}/{alpha}){sub 8}-barrel. Instead, this 'superfamily' may result from assembly from smaller modules, including the conserved phosphate binding motif associated with the C-terminal ({beta}/{alpha}){sub 2}-quarter barrel.« less