2013
DOI: 10.1021/cg400501f
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Heterogeneous Crystallization of Proteins: Is it a Prenucleation Clusters Mediated Process?

Abstract: Several studies have shown that heterogeneous agents are able to reduce required starting protein concentration and induction time for crystallization. However, in many cases, the molecular mechanism by which heterogeneous agents promote the nucleation is still unclear, although examples of epitaxial crystallization have been reported. Here, a set of focused crystallization trials, together with a review of the literature data, point out that the process of heterogeneous nucleation can be described by a noncla… Show more

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Cited by 21 publications
(23 citation statements)
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“…In modern-day terms, we can recognize Turkevich's creative ''Organizer'' hypothesis as analogous to-and really the first instance of-the currently popular concept of ''prenucleation clusters'', namely the assembly of reaction precursors into large macrostructures with longer-range order that are on-path, kinetically viable nuclei able to undergo facile growth. 72 The concept of prenucleation clusters has been increasingly applied in the literature to the following systems: H 2 SO 4 , 73 CaCO 3 , 72,74 homogeneous crystallizations, Na 2 S 2 O 3 , 76 heterogeneous protein crystallization, 77 glass-type transitions in the solid-state, [78][79][80] and most recently Au(0) n nanoparticles. 81 The allure of the prenucleation cluster concept so noted, one critical issue with prenucleation clusters is if the observed clusters are kinetically on, vs. off, path to the final product.…”
Section: A Brief Summary Of Particle-formation Mechanisms Available Since 1952mentioning
confidence: 99%
“…In modern-day terms, we can recognize Turkevich's creative ''Organizer'' hypothesis as analogous to-and really the first instance of-the currently popular concept of ''prenucleation clusters'', namely the assembly of reaction precursors into large macrostructures with longer-range order that are on-path, kinetically viable nuclei able to undergo facile growth. 72 The concept of prenucleation clusters has been increasingly applied in the literature to the following systems: H 2 SO 4 , 73 CaCO 3 , 72,74 homogeneous crystallizations, Na 2 S 2 O 3 , 76 heterogeneous protein crystallization, 77 glass-type transitions in the solid-state, [78][79][80] and most recently Au(0) n nanoparticles. 81 The allure of the prenucleation cluster concept so noted, one critical issue with prenucleation clusters is if the observed clusters are kinetically on, vs. off, path to the final product.…”
Section: A Brief Summary Of Particle-formation Mechanisms Available Since 1952mentioning
confidence: 99%
“…, horse hair, seaweed) which provide nucleation sites for protein crystals despite originating from exogenous materials. 57,58 Further, microseeding as demonstrated on-chip is ideal for applications that require tight control over crystal form and size, such as serial femtosecond crystallography at X-ray free electron lasers, 7,59 and crystallization of proteins for drug delivery. 60,61…”
Section: Discussionmentioning
confidence: 99%
“…The answers to these questions require more work to be done on the characterization of the kinetic signatures associated with different compositions of low-and high-order aggregates (Crespo et al, 2017). Some aspects of nonclassical nucleation mechanisms can be unveiled with the help of advanced microscopic techniques (Fermani et al, 2013). For now, it is important to note the critical role of protein oligomers and metastable clusters in the success of the crystallization step in structural biology pipelines.…”
Section: Possible Mechanism Of Intermittent Crystallizationmentioning
confidence: 99%