Phenamacril: a potent, but reversible, inhibitor of Fusarium class I myosin

Publikation: Bidrag til bog/antologi/rapport/konference proceedingKonferenceabstrakt i proceedingForskning

Resumé

Fungicide application remains a vital component in the management of Fusarium-induced plant infections, but environmental concerns and resistance toward some of the commonly used fungicides has spurred efforts into developing new specific fungicides. Phenamacril, a cyanoacrylate fungicide, represents a novel class of seemingly Fusarium-specific and environmentally benign fungicides that could hold great potential in our future efforts toward minimizing the occurrence and severity of Fusarium-induced plant infections. Phenamacril targets the motor domain of Fusarium class I myosin [1-2], an ubiquitous molecular motor which facilitates numerous ATP-driven and actin-associated processes within the cell. The myosin superfamiliy is divided into approximately 20 different classes (classes I, II, V and XVII are present in fungi), each potentially having several isoforms. While the taskspecific C-terminal tail domains are highly variable in size and function, the N-terminal motor domains remain highly conservered, both structurally and functionally. Interestingly, Phenamacril-resistance has been shown to correlate with single amino acid mutations in a highly conserved region of the motor domain [1], a region involved in the allosteric communication between the actin- and nucleotide binding-site [3]. To gain further insight into the specificity, the inhibitory potential and nature of the Phenamacril-mediated inhibition
of Fusarium myosin, we overexpressed Fusarium class I myosins in Sf9 insect cells. Through a combination of NADH-coupled and in vitro motility assays, we demonstrated that Phenamacril is a very potent but functionally reversible inhibitor of Fusarium class I myosin. Similarly, we demonstrated that Phenamacril had no or only minimal inhibitory effect on human myosin 1c, Dictyostelium discoideum class I and II myosins, but that the motor domain of the Phenamacril-resistant F. solani f. sp. pisi was highly inhibited by Phenamacril in vitro. This suggests that
despite of the high degree of structural conservation in the myosin super-family, subtle differences render Phenamacril a highly specific and potent reversible inhibitor of Fusarium class I myosin.
[1] Zheng Z, Yiping H, Yiqiang C et al (2015): Sci Rep, 5 (2021): 8248.
[2] Zhang C, Yun C, Yanni Y et al (2015): Environ Microbiol, 17 (8): 2735–46.
[3] Krishna C, Taft MH, Martin R et al (2011): J Biol Chem, 286 (34): 29700–708.
OriginalsprogEngelsk
TitelPhenamacril: a potent, but reversible, inhibitor of Fusarium class I myosin
Publikationsdato2018
StatusUdgivet - 2018
BegivenhedEuropean Fusarium Seminar 14 - Tulln, Østrig
Varighed: 8 apr. 201811 apr. 2018

Konference

KonferenceEuropean Fusarium Seminar 14
LokationTulln
LandØstrig
Periode08/04/201811/04/2018

Fingerprint

Myosin Type I
Fusarium
Myosins
Myosin Type II
Cyanoacrylates
Sf9 Cells
Dictyostelium
Infection
NAD
Insects
Tail
Actins
Protein Isoforms
Fungi
Nucleotides
Binding Sites
Communication
Amino Acids

Citer dette

Wollenberg, R., Taft, M. H., Giese, S., Sørensen, J. L., Giese, H., Manstein, D. J., ... Wimmer, R. (2018). Phenamacril: a potent, but reversible, inhibitor of Fusarium class I myosin. I Phenamacril: a potent, but reversible, inhibitor of Fusarium class I myosin
Wollenberg, Rasmus ; Taft, Manuel H ; Giese, Sven ; Sørensen, Jens Laurids ; Giese, Henriette ; Manstein, Dietmar J ; Søndergaard, Teis Esben ; Wimmer, Reinhard. / Phenamacril: a potent, but reversible, inhibitor of Fusarium class I myosin. Phenamacril: a potent, but reversible, inhibitor of Fusarium class I myosin. 2018.
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title = "Phenamacril: a potent, but reversible, inhibitor of Fusarium class I myosin",
abstract = "Fungicide application remains a vital component in the management of Fusarium-induced plant infections, but environmental concerns and resistance toward some of the commonly used fungicides has spurred efforts into developing new specific fungicides. Phenamacril, a cyanoacrylate fungicide, represents a novel class of seemingly Fusarium-specific and environmentally benign fungicides that could hold great potential in our future efforts toward minimizing the occurrence and severity of Fusarium-induced plant infections. Phenamacril targets the motor domain of Fusarium class I myosin [1-2], an ubiquitous molecular motor which facilitates numerous ATP-driven and actin-associated processes within the cell. The myosin superfamiliy is divided into approximately 20 different classes (classes I, II, V and XVII are present in fungi), each potentially having several isoforms. While the taskspecific C-terminal tail domains are highly variable in size and function, the N-terminal motor domains remain highly conservered, both structurally and functionally. Interestingly, Phenamacril-resistance has been shown to correlate with single amino acid mutations in a highly conserved region of the motor domain [1], a region involved in the allosteric communication between the actin- and nucleotide binding-site [3]. To gain further insight into the specificity, the inhibitory potential and nature of the Phenamacril-mediated inhibitionof Fusarium myosin, we overexpressed Fusarium class I myosins in Sf9 insect cells. Through a combination of NADH-coupled and in vitro motility assays, we demonstrated that Phenamacril is a very potent but functionally reversible inhibitor of Fusarium class I myosin. Similarly, we demonstrated that Phenamacril had no or only minimal inhibitory effect on human myosin 1c, Dictyostelium discoideum class I and II myosins, but that the motor domain of the Phenamacril-resistant F. solani f. sp. pisi was highly inhibited by Phenamacril in vitro. This suggests thatdespite of the high degree of structural conservation in the myosin super-family, subtle differences render Phenamacril a highly specific and potent reversible inhibitor of Fusarium class I myosin.[1] Zheng Z, Yiping H, Yiqiang C et al (2015): Sci Rep, 5 (2021): 8248.[2] Zhang C, Yun C, Yanni Y et al (2015): Environ Microbiol, 17 (8): 2735–46.[3] Krishna C, Taft MH, Martin R et al (2011): J Biol Chem, 286 (34): 29700–708.",
author = "Rasmus Wollenberg and Taft, {Manuel H} and Sven Giese and S{\o}rensen, {Jens Laurids} and Henriette Giese and Manstein, {Dietmar J} and S{\o}ndergaard, {Teis Esben} and Reinhard Wimmer",
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Wollenberg, R, Taft, MH, Giese, S, Sørensen, JL, Giese, H, Manstein, DJ, Søndergaard, TE & Wimmer, R 2018, Phenamacril: a potent, but reversible, inhibitor of Fusarium class I myosin. i Phenamacril: a potent, but reversible, inhibitor of Fusarium class I myosin. European Fusarium Seminar 14, Østrig, 08/04/2018.

Phenamacril: a potent, but reversible, inhibitor of Fusarium class I myosin. / Wollenberg, Rasmus; Taft, Manuel H; Giese, Sven; Sørensen, Jens Laurids; Giese, Henriette; Manstein, Dietmar J; Søndergaard, Teis Esben; Wimmer, Reinhard.

Phenamacril: a potent, but reversible, inhibitor of Fusarium class I myosin. 2018.

Publikation: Bidrag til bog/antologi/rapport/konference proceedingKonferenceabstrakt i proceedingForskning

TY - ABST

T1 - Phenamacril: a potent, but reversible, inhibitor of Fusarium class I myosin

AU - Wollenberg, Rasmus

AU - Taft, Manuel H

AU - Giese, Sven

AU - Sørensen, Jens Laurids

AU - Giese, Henriette

AU - Manstein, Dietmar J

AU - Søndergaard, Teis Esben

AU - Wimmer, Reinhard

PY - 2018

Y1 - 2018

N2 - Fungicide application remains a vital component in the management of Fusarium-induced plant infections, but environmental concerns and resistance toward some of the commonly used fungicides has spurred efforts into developing new specific fungicides. Phenamacril, a cyanoacrylate fungicide, represents a novel class of seemingly Fusarium-specific and environmentally benign fungicides that could hold great potential in our future efforts toward minimizing the occurrence and severity of Fusarium-induced plant infections. Phenamacril targets the motor domain of Fusarium class I myosin [1-2], an ubiquitous molecular motor which facilitates numerous ATP-driven and actin-associated processes within the cell. The myosin superfamiliy is divided into approximately 20 different classes (classes I, II, V and XVII are present in fungi), each potentially having several isoforms. While the taskspecific C-terminal tail domains are highly variable in size and function, the N-terminal motor domains remain highly conservered, both structurally and functionally. Interestingly, Phenamacril-resistance has been shown to correlate with single amino acid mutations in a highly conserved region of the motor domain [1], a region involved in the allosteric communication between the actin- and nucleotide binding-site [3]. To gain further insight into the specificity, the inhibitory potential and nature of the Phenamacril-mediated inhibitionof Fusarium myosin, we overexpressed Fusarium class I myosins in Sf9 insect cells. Through a combination of NADH-coupled and in vitro motility assays, we demonstrated that Phenamacril is a very potent but functionally reversible inhibitor of Fusarium class I myosin. Similarly, we demonstrated that Phenamacril had no or only minimal inhibitory effect on human myosin 1c, Dictyostelium discoideum class I and II myosins, but that the motor domain of the Phenamacril-resistant F. solani f. sp. pisi was highly inhibited by Phenamacril in vitro. This suggests thatdespite of the high degree of structural conservation in the myosin super-family, subtle differences render Phenamacril a highly specific and potent reversible inhibitor of Fusarium class I myosin.[1] Zheng Z, Yiping H, Yiqiang C et al (2015): Sci Rep, 5 (2021): 8248.[2] Zhang C, Yun C, Yanni Y et al (2015): Environ Microbiol, 17 (8): 2735–46.[3] Krishna C, Taft MH, Martin R et al (2011): J Biol Chem, 286 (34): 29700–708.

AB - Fungicide application remains a vital component in the management of Fusarium-induced plant infections, but environmental concerns and resistance toward some of the commonly used fungicides has spurred efforts into developing new specific fungicides. Phenamacril, a cyanoacrylate fungicide, represents a novel class of seemingly Fusarium-specific and environmentally benign fungicides that could hold great potential in our future efforts toward minimizing the occurrence and severity of Fusarium-induced plant infections. Phenamacril targets the motor domain of Fusarium class I myosin [1-2], an ubiquitous molecular motor which facilitates numerous ATP-driven and actin-associated processes within the cell. The myosin superfamiliy is divided into approximately 20 different classes (classes I, II, V and XVII are present in fungi), each potentially having several isoforms. While the taskspecific C-terminal tail domains are highly variable in size and function, the N-terminal motor domains remain highly conservered, both structurally and functionally. Interestingly, Phenamacril-resistance has been shown to correlate with single amino acid mutations in a highly conserved region of the motor domain [1], a region involved in the allosteric communication between the actin- and nucleotide binding-site [3]. To gain further insight into the specificity, the inhibitory potential and nature of the Phenamacril-mediated inhibitionof Fusarium myosin, we overexpressed Fusarium class I myosins in Sf9 insect cells. Through a combination of NADH-coupled and in vitro motility assays, we demonstrated that Phenamacril is a very potent but functionally reversible inhibitor of Fusarium class I myosin. Similarly, we demonstrated that Phenamacril had no or only minimal inhibitory effect on human myosin 1c, Dictyostelium discoideum class I and II myosins, but that the motor domain of the Phenamacril-resistant F. solani f. sp. pisi was highly inhibited by Phenamacril in vitro. This suggests thatdespite of the high degree of structural conservation in the myosin super-family, subtle differences render Phenamacril a highly specific and potent reversible inhibitor of Fusarium class I myosin.[1] Zheng Z, Yiping H, Yiqiang C et al (2015): Sci Rep, 5 (2021): 8248.[2] Zhang C, Yun C, Yanni Y et al (2015): Environ Microbiol, 17 (8): 2735–46.[3] Krishna C, Taft MH, Martin R et al (2011): J Biol Chem, 286 (34): 29700–708.

M3 - Conference abstract in proceeding

BT - Phenamacril: a potent, but reversible, inhibitor of Fusarium class I myosin

ER -

Wollenberg R, Taft MH, Giese S, Sørensen JL, Giese H, Manstein DJ et al. Phenamacril: a potent, but reversible, inhibitor of Fusarium class I myosin. I Phenamacril: a potent, but reversible, inhibitor of Fusarium class I myosin. 2018