Scholarlink

<p>Activation of the reverse transsulfuration pathway contributes to the survival and persistence of multidrug-resistant bacteria. The first step of this pathway, catalyzed by the enzyme cystathionine β-synthase (CBS), plays a crucial role in maintaining redox balance and cysteine homeostasis, making it an attractive therapeutic target against multidrug-resistant infections. In this study, we demonstrate that both <i>Pseudomonas aeruginosa</i> CBS and <i>Klebsiella pneumoniae</i> CBS exhibit high responsiveness to the allosteric activator S-adenosylmethionine (SAM) and preferentially utilize O-acetylserine (OAS) as a substrate over serine. The crystal structure of <i>Pa</i>CBS and the AlphaFold-2 model of <i>Kp</i>CBS reveal a novel domain organization characterized by an inverted arrangement of the regulatory Bateman module relative to the catalytic core. These findings provide a new structural and functional basis for the selective inhibition of CBS in multidrug-resistant pathogens.</p>

错误：搜索内容不能为空，请输入英文关键词
错误：关键词超出字数限制，请精简
高级检索

A distinct domain organization of cystathionine β-synthase underlies cysteine and H2S biosynthesis in Pseudomonas aeruginosa and Klebsiella pneumoniae

  • 期刊论文

  • 出版模式：

    开放获取

  • 发表日期：

    2026年6月29日

查看全文
  • Carolina Conter,
  • Reyes Núñez-Franco,
  • Davide Pietrafesa,
  • Carmen Fernández-Rodríguez,
  • Marco Pedretti,
  • Emily Perbellini,
  • Giada Mordenti,
  • Nicola Masè,
  • Paola Dominici,
  • Tomas Majtan,
  • Mattia Falconi,
  • María Luz Martinez-Chantar,
  • Gonzalo Jiménez-Osés,
  • Alessandra Astegno,
  • Luis Alfonso Martínez-Cruz

摘要

Activation of the reverse transsulfuration pathway contributes to the survival and persistence of multidrug-resistant bacteria. The first step of this pathway, catalyzed by the enzyme cystathionine β-synthase (CBS), plays a crucial role in maintaining redox balance and cysteine homeostasis, making it an attractive therapeutic target against multidrug-resistant infections. In this study, we demonstrate that both Pseudomonas aeruginosa CBS and Klebsiella pneumoniae CBS exhibit high responsiveness to the allosteric activator S-adenosylmethionine (SAM) and preferentially utilize O-acetylserine (OAS) as a substrate over serine. The crystal structure of PaCBS and the AlphaFold-2 model of KpCBS reveal a novel domain organization characterized by an inverted arrangement of the regulatory Bateman module relative to the catalytic core. These findings provide a new structural and functional basis for the selective inhibition of CBS in multidrug-resistant pathogens.