AI Article Synopsis
- Isopenicillin synthase (IPNS) catalyzes the transformation of a specific compound (ACV) and dioxygen into isopenicillin, a key ingredient for natural penicillins and cephalosporins.
- Recent studies using advanced techniques like X-ray free-electron lasers show how this reaction leads to changes in the enzyme's shape and behavior, affecting its overall function.
- Findings emphasize the significance of protein movement in facilitating chemical reactions and suggest broader implications for related enzymes in human processes, also showcasing how high-tech crystallography can reveal dynamics in enzyme activities.
Article Abstract
Isopenicillin synthase (IPNS) catalyzes the unique reaction of l-δ-(α-aminoadipoyl)-l-cysteinyl-d-valine (ACV) with dioxygen giving isopenicillin (IPN), the precursor of all natural penicillins and cephalosporins. X-ray free-electron laser studies including time-resolved crystallography and emission spectroscopy reveal how reaction of IPNS:Fe(II):ACV with dioxygen to yield an Fe(III) superoxide causes differences in active site volume and unexpected conformational changes that propagate to structurally remote regions. Combined with solution studies, the results reveal the importance of protein dynamics in regulating intermediate conformations during conversion of ACV to IPN. The results have implications for catalysis by multiple IPNS-related oxygenases, including those involved in the human hypoxic response, and highlight the power of serial femtosecond crystallography to provide insight into long-range enzyme dynamics during reactions presently impossible for nonprotein catalysts.
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| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8378823 | PMC |
| http://dx.doi.org/10.1126/sciadv.abh0250 | DOI Listing |
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