Brownian dynamics of interactions between aldolase mutants and F‐actin

Lowe, Stephen L.; Atkinson, Derek M.; Waingeh, Victor F.; Thomasson, Kathryn A.

doi:10.1002/jmr.599

Cited by 12 publications

(20 citation statements)

References 48 publications

(71 reference statements)

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“…As observed in previous simulations with rabbit aldolase, 10,12 the minimum in the free energy curves for simulations with both fish and human aldolase occur when the center of mass of either aldolase molecule is 83-85 Å from the F-actin helical axis. The calculated radial binding free energies during docking were À1.5 6 0.03 kcal/mol (fish), À2.27 6 0.05 kcal/mol (human), and À2.0 6 0.04 kcal/mol (rabbit).…”

Section: Bd Simulation Of Free Energy Of Interactionsupporting

confidence: 79%

“…Lowe et al, from mutation studies with rabbit aldolase, predicted that there is no simple correlation between the net charge of the enzymes and binding. 12 Previous BD simulations by Lowe et al observed no well depth (greatly reduced binding) in the interaction involving rabbit aldolase, when important residues (Lys 341, Lys 288, and Lys 293) were mutated to alanines. 12 They also showed that the mutation of Lys 341 affected binding greatest.…”

Section: 2mentioning

confidence: 93%

“…12 Previous BD simulations by Lowe et al observed no well depth (greatly reduced binding) in the interaction involving rabbit aldolase, when important residues (Lys 341, Lys 288, and Lys 293) were mutated to alanines. 12 They also showed that the mutation of Lys 341 affected binding greatest. Likewise Scatchard analysis based on copelleting experiments compared the affinity of aldolase binding to both wild type and mutant forms of actin.…”

Section: 2mentioning

confidence: 93%

“…Previous Brownian dynamics (BD) simulations with rabbit aldolase and glyceraldehydye phosphate dehydrogenase (GAPDH) have determined binding modes with F-actin and reproduced their relative binding affinities. [10][11][12][13][14] The advantage of these theoretical methods is that they provide an atomistic description of these interactions. BD studies have shown that the F-actin binding site on aldolase is distinct from the active site of the enzyme, and it involves the positive grooves formed between subunits A/D and B/C.…”

Section: Theoretical Study Of Interactions Between Muscle Aldolase Anmentioning

confidence: 99%

“…The calculated radial binding free energies during docking were À1.5 6 0.03 kcal/mol (fish), À2.27 6 0.05 kcal/mol (human), and À2.0 6 0.04 kcal/mol (rabbit). 10,12 Also shown in Figure 10a is an entropic curve (-TS) for simulations with both human and fish aldolase, The energy describes the specific electrostatic interaction energy between the two proteins. Each residue is identified by the three-letter code for the amino acid followed by the residue number with subunit identification.…”

Section: Bd Simulation Of Free Energy Of Interactionmentioning

confidence: 99%

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Theoretical study of interactions between muscle aldolase and F‐actin: Insight into different species

Forlemu¹,

Waingeh²,

Ouporov³

et al. 2006

Biopolymers

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Interactions of the glycolytic enzyme, fructose‐1,6‐bisphosphate aldolase (aldolase), with F‐actin may be one mechanism for the colocalization of glycolytic enzymes. Examination of these interactions in different animal species tests this hypothesis by observing whether binding sites are conserved across species. Brownian dynamics (BD) simulations provide descriptions of such protein–protein interactions with the muscle isoforms of zebra fish and human aldolase. The results are compared with previous results obtained for rabbit muscle and yeast. The aldolase binding groove previously determined in rabbit muscle is conserved in both the human and fish muscle isoforms. The nonspecific radial free energies of interaction are similar with fish being slightly weaker than human and rabbit: human, −2.27 ± 0.05 kcal/mol; rabbit, −2.0 ± 0.04 kcal/mol; and fish, −1.5 ± 0.03 kcal/mol. BD results show a large Boltzmann population of complexes formed around the A/D and B/C grooves of aldolase with the most feasible binding mode comprising two aldolase subunits to subdomain I region of the actin subunits. These results show that the location of the important residues and binding site for fish and human aldolase is very similar to that in rabbit and that in different animals the binding site is conserved. This suggests that the binding interaction between aldolase and F‐actin is general in animal muscles and is rendered possible and energetically favorable through the conservation of this binding site. © 2006 Wiley Periodicals, Inc. Biopolymers 85: 60–71, 2007.This article was originally published online as an accepted preprint. The “Published Online” date corresponds to the preprint version. You can request a copy of the preprint by emailing the Biopolymers editorial office at biopolymers@wiley.com

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Section: Bd Simulation Of Free Energy Of Interactionsupporting

confidence: 79%

Section: 2mentioning

confidence: 93%

Section: 2mentioning

confidence: 93%

Section: Theoretical Study Of Interactions Between Muscle Aldolase Anmentioning

confidence: 99%

Section: Bd Simulation Of Free Energy Of Interactionmentioning

confidence: 99%

See 3 more Smart Citations

Theoretical study of interactions between muscle aldolase and F‐actin: Insight into different species

Forlemu¹,

Waingeh²,

Ouporov³

et al. 2006

Biopolymers

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Brownian dynamics simulations of glycolytic enzyme subsets with F‐actin

et al. 2003

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Previous Brownian dynamics (BD) simulations identified specific basic residues on fructose-1,6-bisphophate aldolase (aldolase) (I. V. Ouporov et al., Biophysical Journal, 1999, Vol. 76, pp. 17-27) and glyceraldehyde-3-phosphate dehydrogenase (GAPDH) (I. V. Ouporov et al., Journal of Molecular Recognition, 2001, Vol. 14, pp. 29-41) involved in binding F-actin, and suggested that the quaternary structure of the enzymes may be important. Herein, BD simulations of F-actin binding by enzyme dimers or peptides matching particular sequences of the enzyme and the intact enzyme triose phosphate isomerase (TIM) are compared. BD confirms the experimental observation that TIM has little affinity for F-actin. For aldolase, the critical residues identified by BD are found in surface grooves, formed by subunits A/D and B/C, where they face like residues of the neighboring subunit enhancing their electrostatic potentials. BD simulations between F-actin and aldolase A/D dimers give results similar to the native tetramer. Aldolase A/B dimers form complexes involving residues that are buried in the native structure and are energetically weaker; these results support the importance of quaternary structure for aldolase. GAPDH, however, placed the critical residues on the corners of the tetramer so there is no enhancement of the electrostatic potential between the subunits. Simulations using GAPDH dimers composed of either S/H or G/H subunits show reduced binding energetics compared to the tetramer, but for both dimers, the sets of residues involved in binding are similar to those found for the native tetramer. BD simulations using either aldolase or GAPDH peptides that bind F-actin experimentally show complex formation. The GAPDH peptide bound to the same F-actin domain as did the intact tetramer; however, unlike the tetramer, the aldolase peptide lacked specificity for binding a single F-actin domain.

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Brownian dynamics of interactions between glyceraldehyde‐3‐phosphate dehydrogenase (GAPDH) mutants and F‐actin

2004

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Brownian dynamics simulations of computer models of GAPDH mutants interacting with F-actin emphasized the electrostatic nature of such interactions, and confirmed the importance of four previously identified lysine residues on the GAPDH structure in these interactions. Mutants were GAPDH models in which one or more of the previously identified lysines had been replaced with alanine. Simulations showed reduced binding of these mutants to F-actin compared to wild-type GAPDH. Binding was significantly reduced by mutating the four lysines; the specific electrostatic interaction energy of the quadruple mutant was -7.3 +/- 1.0 compared to -11.4 +/- 0.5 kcal/mol for the wild enzyme. The BD simulations also reaffirmed the importance of quaternary structure for GAPDH binding F-actin.

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Brownian dynamics of interactions between aldolase mutants and F‐actin

Cited by 12 publications

References 48 publications

Theoretical study of interactions between muscle aldolase and F‐actin: Insight into different species

Theoretical study of interactions between muscle aldolase and F‐actin: Insight into different species

Brownian dynamics simulations of glycolytic enzyme subsets with F‐actin

Brownian dynamics of interactions between glyceraldehyde‐3‐phosphate dehydrogenase (GAPDH) mutants and F‐actin

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