Inside Back Cover: Flipping of a Nonproductive Substrate Binding Conformation Facilitates Hydroxynitrile Lyase Catalyzed Hydrocyanation (Angew. Chem. Int. Ed. 52/2025)
Conformational interchange of enzyme–substrate complexes are intrinsic to catalysis, yet their transient nature makes it elusive for understanding the substrate conformational dynamics. In the Research Article (e15778) by Yi-Lei Zhao, Hui-Lei Yu, and co-workers a “flipped” substrate binding conformation in the hydroxynitrile lyase from Prunus communis (PcHNL5) is revealed. Crystallographic and computational analyses show that this non-productive state must reorganize before catalysis proceeds. Mutagenesis destabilizes this non-productive conformation, promoting conversion to the productively competent state and markedly enhancing enzymatic efficiency.
Authors
- Fulong Li (ORCID: https://orcid.org/0000-0002-2460-3266)
- Zhi‐Jun Zhang (ORCID: https://orcid.org/0000-0001-9836-0204)
- Yong Mao (ORCID: https://orcid.org/0000-0001-9268-4523)
- Qiang Geng (ORCID: https://orcid.org/0000-0003-2842-8263)
- Yu‐Cong Zheng (ORCID: https://orcid.org/0000-0001-8509-3127)
- Xu‐Dong Kong (ORCID: https://orcid.org/0000-0003-3216-7545)
- Jian‐He Xu (ORCID: https://orcid.org/0000-0003-4301-7630)
- Rong Ran (ORCID: https://orcid.org/0000-0001-9904-8896)
- Yi‐Lei Zhao (ORCID: https://orcid.org/0000-0003-4687-7847)
- Hui‐Lei Yu (ORCID: https://orcid.org/0000-0002-1925-3679)
- Qi Chen (ORCID: https://orcid.org/0000-0002-1287-2557)
- Lin Zhang (ORCID: https://orcid.org/0000-0002-5269-9728)
- Yizhou Qi (ORCID: https://orcid.org/0000-0001-7981-5488)
Institutions
- East China University of Science and Technology (CN)
- Shanghai Jiao Tong University (CN)
- Shanghai Institute of Organic Chemistry (CN)
Publication Details
- Journal
- Angewandte Chemie International Edition
- Published
- 2025-11-23
- DOI
- https://doi.org/10.1002/anie.2025-m1711061800
- Primary Topic
- Enzyme Catalysis and Immobilization
- Type
- article
- Field-Weighted Citation Impact
- 0.00