Biological complexity: enzyme complexity (Introduction)

by David Turell , Tuesday, December 17, 2019, 19:05 (1590 days ago) @ David Turell

More on how enzymes work:

https://phys.org/news/2019-12-reveal-enzyme-motions-catalyze-reactions.html

"In a time-resolved X-ray experiment, researchers uncovered, at atomic resolution and in real time, the previously unknown way that a microbial enzyme breaks down organic compounds.

"The team, led by Mark Wilson at the University of Nebraska Lincoln (UNL) and Henry van den Bedem at the Department of Energy's SLAC National Accelerator Laboratory (now at Atomwise Inc.), published their findings last week in the Proceedings of the National Academy of Sciences. What they learned about this enzyme, whose structure is similar to one that is implicated in neurodegenerative diseases such as Parkinson's, could lead to a better understanding of how antibiotics are broken down by microbes and to the development of more effective drugs.

"Previously, the researchers used SLAC's Stanford Synchrotron Radiation Lightsource (SSRL) to obtain the structure of the enzyme at very low temperatures using X-ray crystallography. In this study, Medhanjali Dasgupta, a UNL graduate student who was the study's first author, used the Linac Coherent Light Source (LCLS), SLAC's X-ray laser, to watch the enzyme and its substrate within the crystal move and change as it went through a full catalytic cycle at room temperature.

"The scientists used special software, designed by van den Bedem, that is highly sensitive to identifying protein movement from X-ray crystallography data to interpret the results, revealing never-before-seen motions that play a key role in catalyzing complex reactions, such as breaking down antibiotics. Next, the researchers hope to use LCLS to obtain room temperature structures of other enzymes to get a better look at how the motions occurring within them help move along reactions."

Comment: See the diagrams to learn how the enzyme changes chemical bonds to achieve the new reaction. Without enzymes there would be no biochemical activity and life would not exist. Enzyme molecular complexity requires design. From the journal itself:

"Significance
Protein structures fluctuate owing to thermal motion and in response to functional changes such as ligand binding. As a consequence, it is challenging to determine which protein motions are functionally most important at equilibrium. Enzymes that are transiently covalently modified during catalysis offer a way to identify functional motions, as the modification can trigger catalytically important conformational changes. The covalent modification of the active-site cysteine in isocyanide hydratase weakens a critical hydrogen bond required for reactivity. Hydrogen bond disruption triggers a cascade of conformational changes whose modulation by mutation is detrimental to enzyme turnover. Most enzymes that form catalytic intermediates will experience similar transient changes in active-site electrostatics, suggesting that modification-gated conformational dynamics is common in enzymes."