.png){kind=icon}
.png){kind=icon}
Return
Thermally Induced Conformation Remodeling Remarkably Boosts Cytochrome c Activity
.png){kind=icon}
PRE
AI
L
Y
D
DOI：10.1021/acs.jpcb.6c00002.png)
.png){kind=icon}
Original request for help.png){kind=icon}
Share.png){kind=icon}
Save
Abstract
En 中文
Boosting the catalytic performance of an enzyme through controlled conformational regulation in vitro remains challenging due to its intrinsic structural complexity and conformational instability. Herein, we report a straightforward thermal activation strategy that induces permanent conformational remodeling of cytochrome c (Cyt c) toward a catalytically favorable state. The activated Cyt c exhibits up to 4.4-fold biocatalytic activity enhancement compared to the native enzyme and maintains its full activity over at least 7 days of storage. Mechanistic investigations combining experimental characterization and molecular simulations reveal that activity enhancement is governed by a well-defined structural evolution at the molecular level. Thermal activation drives a local unfolding-refolding transition in the vicinity of the catalytic center, leading to the opening of the catalytic gate and a pronounced increase in substrate accessibility. Simultaneously, the coordination environment between heme Fe and Met80 S changes to a relaxed conformation, whereas the Fe-N (His18) coordination remains relatively rigid during the thermal activation. This asymmetric coordination modulation establishes a balanced heme microenvironment that ensures both high substrate accessibility and structural integrity of the heme center, thus enabling efficient catalysis without compromising robustness. These findings elucidate a clear structure-activity relationship linking thermally induced conformational evolution to enhanced enzyme-substrate interactions and catalytic performance and demonstrate thermal activation as an effective strategy for modulating metalloenzyme catalysis.
Keywords:
GPU NODES
BANG
Journal
IF:
2.9
Papers:
1.4K
Citations:
9.0W
Organization
Cited Papers