Analysis of residuals from enzyme kinetic and protein folding experiments in the presence of correlated experimental noise

Kuzmič, Petr; Lorenz, Thorsten; Reinstein, Jochen

doi:10.1016/j.ab.2009.05.051

Cited by 9 publications

(7 citation statements)

References 13 publications

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“…A pattern of residual signs of the kind [þ --þþþþþ], from independent measurements, is considered as random, whereas a pattern like this [--þþþþþþ--] is not. Though a formal statistical test may carry out [94] with the information afforded by the residual plot, it is necessary a number of points greater than is usual in calibrate measurements.…”

Section: Linearity In Calibration Methods: Fluorescence Data As Examplementioning

confidence: 99%

Fitting Models to Data: Residual Analysis, a Primer

Martín¹,

Adana²,

Asuero³

2017

Uncertainty Quantification and Model Calibration

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Section: Linearity In Calibration Methods: Fluorescence Data As Examplementioning

confidence: 99%

Fitting Models to Data: Residual Analysis, a Primer

Martín¹,

Adana²,

Asuero³

2017

Uncertainty Quantification and Model Calibration

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“…In general, larger effects were observed at lower levels of basal autophosphorylation. The progress curves were fit to an autocatalytic model in DynaFit ( Kuzmic, 2009 ; Kuzmic et al. , 2009 ; Figure 3B–E ).…”

Section: Resultsmentioning

confidence: 99%

Hydrostatic Pressure Sensing by WNK kinases

Humphreys

Teixeira

Akella

et al. 2023

MBoC

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Previous work has demonstrated that the WNK kinases 1 and 3 are direct osmosensors consistent with their established role in cell volume control. WNK kinases may also be regulated by hydrostatic pressure. Hydrostatic pressure applied to cells in culture with N2 gas or to Drosophila Malpighian tubules by centrifugation induces phosphorylation of downstream effectors of endogenous WNKs. In vitro, the autophosphorylation and activity of the unphosphorylated kinase domain of WNK3 (uWNK3) is enhanced to a lesser extent than in cells by 190 kPa applied with N2 gas. Hydrostatic pressure measurably alters the structure of uWNK3. Data from size exclusion chromatography in line with multi-angle light scattering (SEC-MALS), SEC alone at different back pressures, analytical ultracentrifugation (AUC), NMR, and chemical crosslinking indicate a change in oligomeric structure in the presence of hydrostatic pressure from a WNK3 dimer to a monomer. The effects on the structure are related to those seen with osmolytes. Potential mechanisms of hydrostatic pressure activation of uWNK3 and the relationships of pressure activation to WNK osmosensing are discussed.

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“…Conventional analysis was useful for defining the basic reaction mechanism (number of steps) and for providing initial estimates of the rate constants for each step. However, as noted by Johnson , and others ,, , conventional analysis ignores some of the information content in kinetic data (e.g., reaction amplitudes) and does not facilitate integration of multiple kinds of kinetic data (e.g., binding data and dissociation data), so it is important to supplement conventional analysis with some kind of global analysis that can overcome these limitations. This is especially true for multistep reaction mechanisms that can give rise to nonintuitive results.…”

Section: Resultsmentioning

confidence: 99%

“…The benefits of using computer simulations to support and extend conventional kinetic analysis have been recognized since the 1970s, but this approach did not become “mainstream” because it required prohibitive levels of computer expertise and hardware. With recent advances in personal computer speed and the availability of powerful but user-friendly software packages, these barriers have been largely eliminated − ,,, , enabling what Johnson and co-workers have termed the “New Enzymology”. This new level of analysis has provided some sobering examples of how conventional analysis, in the absence of any accompanying global analysis, can be extremely misleading , .…”

Section: Discussionmentioning

confidence: 99%

Kinetics of ATP and TNP-ATP Binding to the Active Site of CheA from Thermotoga maritima

Eaton

Stewart

2010

Biochemistry

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The mechanism of nucleotide binding to the active site of Thermotoga maritima CheA was investigated using stopped-flow fluorescence experiments that monitored binding of ATP and TNP-ATP to the catalytic domain (P4) of CheA that had been engineered to include a tryptophan residue as a fluorescent reporter group at the active site (P4(F487W)). Rapid decreases in protein intrinsic fluorescence and increases in TNP-ATP fluorescence were observed during binding reactions, and time courses were analyzed to define the kinetic mechanisms for ATP and TNP-ATP binding. This analysis indicated that binding of ATP(Mg(2+)) to P4(F487W) involves a single reversible step with a k(on) of 0.92 +/- 0.09 microM(-1) s(-1), a k(off) of 1.9 +/- 0.4 s(-1), and a K(d) of 1.5-2.1 microM (all values determined at 4 degrees C). Binding of TNP-ATP(Mg(2+)) to P4(F487W) involves a more complicated mechanism, requiring at least three sequential steps. Computer simulations and nonlinear regression analysis were used to estimate the rate constants of the forward and reverse reactions for each of the three steps in the reaction scheme [Formula: see text] Similar analysis indicated that an alternative reaction scheme, involving a rate-limiting conformational change in P4 prior to TNP-ATP binding, did an equally good job of accounting for all of the kinetics results:[Formula: see text] In both models, steps 2 and 3 have slow reversal rates that contribute to the high affinity of the active site for TNP-ATP (K(d) = 0.015 microM). These results highlight the dramatic effect of the TNP moieties on CheA-nucleotide interactions, and they provide the first detailed information about the kinetic mechanism underlying interaction of a protein histidine kinase with this tight-binding inhibitor.

show abstract

Analysis of residuals from enzyme kinetic and protein folding experiments in the presence of correlated experimental noise

Cited by 9 publications

References 13 publications

Fitting Models to Data: Residual Analysis, a Primer

Fitting Models to Data: Residual Analysis, a Primer

Hydrostatic Pressure Sensing by WNK kinases

Kinetics of ATP and TNP-ATP Binding to the Active Site of CheA from Thermotoga maritima

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