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Linking Protein Dynamics to Function
Author(s) -
Klinman Judith P.
Publication year - 2007
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.21.5.a645-d
Subject(s) - chemistry , active site , protein dynamics , catalysis , enzyme catalysis , molecular dynamics , protein function , protein structure , hydride , stereochemistry , chemical physics , computational chemistry , metal , biochemistry , organic chemistry , gene
Although it is well accepted that protein conformational changes play an essential role in enzyme catalysis, the link between protein motion and the making and breaking of chemical bonds is more controversial. The increasingly widespread evidence for hydrogen tunneling in enzyme catalyzed C‐H abstraction reactions provides a powerful platform for investigating catalytically relevant protein dynamics. This is because the barrier that controls H‐tunneling comes from the surrounding heavy atom environment. Using evidence for enzymes that catalyze hydride transfer, a new model is advanced that invokes two types of protein motions in catalysis: these are termed preorganization and reorganization. Preorganization is largely an entropic term that represents the interconversion of protein among many substates, with a small number of these substates having the correct interactions for catalysis. Reorganization represents the actual barrier within the correctly preorganized states and is expected to be dominated by an enthalpic term. One dominant feature to emerge is that while protein flexibility is required for the preorganization event, effective preorganization is correlated with rigidity at the active site. Introduction of alterations in protein structure, substrate structure or reaction conditions can lead to an impaired preorganization and the requirement for an active site with greater mobility. (Supported by NIH GM25765 and NSF MCB 0446395)