Structured crowding and its effects on enzyme catalysis

Buyong Ma*, Ruth Nussinov

*Corresponding author for this work

Research output: Chapter in Book/Report/Conference proceedingChapterpeer-review

31 Scopus citations


Macromolecular crowding decreases the diffusion rate, shifts the equilibrium of protein-protein and protein-substrate interactions, and changes protein conformational dynamics. Collectively, these effects contribute to enzyme catalysis. Here we describe how crowding may bias the conformational change and dynamics of enzyme populations and in this way affect catalysis. Crowding effects have been studied using artificial crowding agents and in vivo-like environments. These studies revealed a correlation between protein dynamics and function in the crowded environment. We suggest that crowded environments be classified into uniform crowding and structured crowding. Uniform crowding represents random crowding conditions created by synthetic particles with a narrow size distribution. Structured crowding refers to the highly coordinated cellular environment, where proteins and other macromolecules are clustered and organized. In structured crowded environments the perturbation of protein thermal stability may be lower; however, it may still be able to modulate functions effectively and dynamically. Dynamic, allosteric enzymes could be more sensitive to cellular perturbations if their free energy landscape is flatter around the native state; on the other hand, if their free energy landscape is rougher, with high kinetic barriers separating deep minima, they could be more robust. Above all, cells are structured; and this holds both for the cytosol and for the membrane environment. The crowded environment is organized, which limits the search, and the crowders are not necessarily inert. More likely, they too transmit allosteric effects, and as such play important functional roles. Overall, structured cellular crowding may lead to higher enzyme efficiency and specificity.

Original languageEnglish
Title of host publicationDynamics in Enzyme Catalysis
EditorsJudith Klinman, Sharon Hammes-Schiffer
Number of pages16
StatePublished - 2013

Publication series

NameTopics in Current Chemistry
ISSN (Print)0340-1022


FundersFunder number
National Institutes of HealthHHSN261200800001E
National Cancer InstituteZIABC010441


    • Allostery
    • Conformational selection
    • Energy landscape
    • Enzymatics
    • Macromolecular crowding
    • Protein dynamics


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