6EOA

Crystal Structure of HAL3 from Cryptococcus neoformans

6EOA の概要

• エントリーDOI: 10.2210/pdb6eoa/pdb
• 分子名称: Phosphopantothenoylcysteine decarboxylase, FLAVIN MONONUCLEOTIDE (3 entities in total)
• 機能のキーワード: fmn, phosphopantothenoylcysteine decarboxylase (ppcdc) enzyme, flavoprotein
• 由来する生物種: Cryptococcus neoformans
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 35556.78

構造登録者

Reverter, D.,Zhang, C.,Molero, C.,Arino, J. (登録日: 2017-10-09, 公開日: 2018-10-31, 最終更新日: 2024-01-17)

主引用文献

Zhang, C.,Garcia-Rodas, R.,Molero, C.,de Oliveira, H.C.,Tabernero, L.,Reverter, D.,Zaragoza, O.,Arino, J.
Characterization of the atypical Ppz/Hal3 phosphatase system from the pathogenic fungus Cryptococcus neoformans.
Mol.Microbiol., 111:898-917, 2019

PubMed Abstract: Ppz Ser/Thr protein phosphatases (PPases) are found only in fungi and have been proposed as potential antifungal targets. In Saccharomyces cerevisiae Ppz1 (ScPpz1) is involved in regulation of monovalent cation homeostasis. ScPpz1 is inhibited by two regulatory proteins, Hal3 and Vhs3, which have moonlighting properties, contributing to the formation of an unusual heterotrimeric PPC decarboxylase (PPCDC) complex crucial for CoA biosynthesis. Here we report the functional characterization of CnPpz1 (CNAG_03673) and two possible Hal3-like proteins, CnHal3a (CNAG_00909) and CnHal3b (CNAG_07348) from the pathogenic fungus Cryptococcus neoformans. Deletion of CnPpz1 or CnHal3b led to phenotypes unrelated to those observed in the equivalent S. cerevisiae mutants, and the CnHal3b-deficient strain was less virulent. CnPpz1 is a functional PPase and partially replaced endogenous ScPpz1. Both CnHal3a and CnHal3b interact with ScPpz1 and CnPpz1 in vitro but do not inhibit their phosphatase activity. Consistently, when expressed in S. cerevisiae, they poorly reproduced the Ppz1-regulatory properties of ScHal3. In contrast, both proteins were functional monogenic PPCDCs. The CnHal3b isoform was crystallized and, for the first time, the 3D-structure of a fungal PPCDC elucidated. Therefore, our work provides the foundations for understanding the regulation and functional role of the Ppz1-Hal3 system in this important pathogenic fungus.

PubMed: 30536975
DOI: 10.1111/mmi.14181

実験手法

X-RAY DIFFRACTION (2.18 Å)