Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:3.6.4.4 (kinesin)
 5,033 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We studied fluctuations in the displacement of silica beads driven by single molecules of the motor protein kinesin, moving under low mechanical loads at saturating ATP concentrations. The variance in position was significantly smaller than expected for the case of stepwise movement along a regular lattice of positions with exponentially distributed intervals. The small variance suggests that two or more sequential processes with comparable reaction rates dominate the biochemical cycle. The low value is inconsistent with certain recently proposed thermal ratchet models for motor movement as well as with scenarios where the hydrolysis of a single ATP molecule leads to a cluster of several steps. Fluctuation analysis is a potential powerful tool for studying kinetic behavior whenever the output of a single enzyme can be monitored.
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PMID:Fluctuation analysis of motor protein movement and single enzyme kinetics. 799 36

With every step it takes, the kinesin motor undergoes a mechanochemical reaction cycle that includes the hydrolysis of one ATP molecule, ADPP(i) release, plus an unknown number of additional transitions. Kinesin velocity depends on both the magnitude and the direction of the applied load. Using specialized apparatus, we subjected single kinesin molecules to forces in differing directions. Sideways and forward loads up to 8 pN exert only a weak effect, whereas comparable forces applied in the backward direction lead to stall. This strong directional bias suggests that the primary working stroke is closely aligned with the microtubule axis. Sideways loads slow the motor asymmetrically, but only at higher ATP levels, revealing the presence of additional, load-dependent transitions late in the cycle. Fluctuation analysis shows that the cycle contains at least four transitions, and confirms that hydrolysis remains tightly coupled to stepping. Together, our findings pose challenges for models of kinesin motion.
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PMID:Probing the kinesin reaction cycle with a 2D optical force clamp. 1259 57

We investigate theoretically the violations of Einstein and Onsager relations and the thermodynamic efficiency for a single processive motor operating far from equilibrium using an extension of the two-state model introduced by Kafri et al. [Biophys. J. 86, 3373 (2004)10.1529/biophysj.103.036152]. With the aid of the Fluctuation Theorem, we analyze the general features of these violations and this efficiency and link them to mechanochemical couplings of motors. In particular, an analysis of the experimental data of kinesin using our framework leads to interesting predictions that may serve as a guide for future experiments.
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PMID:Nonequilibrium fluctuations and mechanochemical couplings of a molecular motor. 1799 15

The Harada-Sasa equality elegantly connects the energy dissipation rate of a moving object with its measurable violation of the Fluctuation-Dissipation Theorem (FDT). Although proven for Langevin processes, its validity remains unclear for discrete Markov systems whose forward and backward transition rates respond asymmetrically to external perturbation. A typical example is a motor protein called kinesin. Here we show generally that the FDT violation persists surprisingly in the high-frequency limit due to the asymmetry, resulting in a divergent FDT violation integral and thus a complete breakdown of the Harada-Sasa equality. A renormalized FDT violation integral still well predicts the dissipation rate when each discrete transition produces a small entropy in the environment. Our study also suggests a way to infer this perturbation asymmetry based on the measurable high-frequency-limit FDT violation.
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PMID:Inferring energy dissipation from violation of the fluctuation-dissipation theorem. 2990 3