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Moving through Barriers: Unlocking the Mysteries of How Enzymes Really Work
Author(s) -
Klinman Judith
Publication year - 2015
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.29.1_supplement.100.1
Subject(s) - flexibility (engineering) , nanotechnology , active site , chemistry , computational biology , enzyme , biology , biochemistry , materials science , statistics , mathematics
Delineating the physical principles that underlie enzyme catalysis remains a major challenge at the biology/chemistry interface. Recent investigations in enzymology have moved beyond the historical focus on “transition state stabilization”, toward an understanding of the important interplay between protein motions and the generation of highly precise active site interactions. The almost universal contribution of nuclear tunneling to enzymatic C‐H activation reactions offers an especially powerful tool to quantify the role of reduced barrier width in catalysis and its inherent link to enzyme flexibility. The ability to detect positionally specific networks of protein motions implicates an evolutionary tuning of large regions of the protein that extend beyond the active site. These studies are beginning to uncover design principles for the generation of de novo catalysts. (Supported by funding from the NIH, GM025765)