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Defluorination Capability of l-2-Haloacid Dehalogenases in the HAD-Like Hydrolase Superfamily Correlates with Active Site Compactness

Research output: Contribution to journal › Article › peer-review

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Defluorination Capability of l-2-Haloacid Dehalogenases in the HAD-Like Hydrolase Superfamily Correlates with Active Site Compactness. / Chan, Peter W Y; Chakrabarti, Nilmadhab; Ing, Chris et al.
In: ChemBioChem, Vol. 23, No. 1, e202100414, 05.01.2022.

Research output: Contribution to journal › Article › peer-review

HarvardHarvard

Chan, PWY, Chakrabarti, N, Ing, C, Halgas, O, To, TKW, Wälti, M, Petit, A-P, Tran, C, Savchenko, A, Yakunin, AF, Edwards, EA, Pomès, R & Pai, EF 2022, 'Defluorination Capability of l-2-Haloacid Dehalogenases in the HAD-Like Hydrolase Superfamily Correlates with Active Site Compactness', ChemBioChem, vol. 23, no. 1, e202100414. https://doi.org/10.1002/cbic.202100414

APA

Chan, P. W. Y., Chakrabarti, N., Ing, C., Halgas, O., To, T. K. W., Wälti, M., Petit, A.-P., Tran, C., Savchenko, A., Yakunin, A. F., Edwards, E. A., Pomès, R., & Pai, E. F. (2022). Defluorination Capability of l-2-Haloacid Dehalogenases in the HAD-Like Hydrolase Superfamily Correlates with Active Site Compactness. ChemBioChem, 23(1), Article e202100414. https://doi.org/10.1002/cbic.202100414

CBE

Chan PWY, Chakrabarti N, Ing C, Halgas O, To TKW, Wälti M, Petit A-P, Tran C, Savchenko A, Yakunin AF, et al. 2022. Defluorination Capability of l-2-Haloacid Dehalogenases in the HAD-Like Hydrolase Superfamily Correlates with Active Site Compactness. ChemBioChem. 23(1):Article e202100414. https://doi.org/10.1002/cbic.202100414

MLA

Chan, Peter W Y et al. "Defluorination Capability of l-2-Haloacid Dehalogenases in the HAD-Like Hydrolase Superfamily Correlates with Active Site Compactness". ChemBioChem. 2022. 23(1). https://doi.org/10.1002/cbic.202100414

VancouverVancouver

Chan PWY, Chakrabarti N, Ing C, Halgas O, To TKW, Wälti M et al. Defluorination Capability of l-2-Haloacid Dehalogenases in the HAD-Like Hydrolase Superfamily Correlates with Active Site Compactness. ChemBioChem. 2022 Jan 5;23(1):e202100414. doi: 10.1002/cbic.202100414

Author

Chan, Peter W Y ; Chakrabarti, Nilmadhab ; Ing, Chris et al. / Defluorination Capability of l-2-Haloacid Dehalogenases in the HAD-Like Hydrolase Superfamily Correlates with Active Site Compactness. In: ChemBioChem. 2022 ; Vol. 23, No. 1.

RIS

TY - JOUR

T1 - Defluorination Capability of l-2-Haloacid Dehalogenases in the HAD-Like Hydrolase Superfamily Correlates with Active Site Compactness

AU - Chan, Peter W Y

AU - Chakrabarti, Nilmadhab

AU - Ing, Chris

AU - Halgas, Ondrej

AU - To, Terence K W

AU - Wälti, Marielle

AU - Petit, Alain-Pierre

AU - Tran, Christopher

AU - Savchenko, Alexei

AU - Yakunin, Alexander F

AU - Edwards, Elizabeth A

AU - Pomès, Régis

AU - Pai, Emil F

N1 - © 2021 Wiley-VCH GmbH.

PY - 2022/1/5

Y1 - 2022/1/5

N2 - l-2-Haloacid dehalogenases, industrially and environmentally important enzymes that catalyse cleavage of the carbon-halogen bond in S-2-halocarboxylic acids, were known to hydrolyse chlorinated, brominated and iodinated substrates but no activity towards fluorinated compounds had been reported. A screen for novel dehalogenase activities revealed four l-2-haloacid dehalogenases capable of defluorination. We now report crystal structures for two of these enzymes, Bpro0530 and Rha0230, as well as for the related proteins PA0810 and RSc1362, which hydrolyse chloroacetate but not fluoroacetate, all at ∼2.2 Å resolution. Overall structure and active sites of these enzymes are highly similar. In molecular dynamics (MD) calculations, only the defluorinating enzymes sample more compact conformations, which in turn allow more effective interactions with the small fluorine atom. Structural constraints, based on X-ray structures and MD calculations, correctly predict the defluorination activity of the homologous enzyme ST2570.

AB - l-2-Haloacid dehalogenases, industrially and environmentally important enzymes that catalyse cleavage of the carbon-halogen bond in S-2-halocarboxylic acids, were known to hydrolyse chlorinated, brominated and iodinated substrates but no activity towards fluorinated compounds had been reported. A screen for novel dehalogenase activities revealed four l-2-haloacid dehalogenases capable of defluorination. We now report crystal structures for two of these enzymes, Bpro0530 and Rha0230, as well as for the related proteins PA0810 and RSc1362, which hydrolyse chloroacetate but not fluoroacetate, all at ∼2.2 Å resolution. Overall structure and active sites of these enzymes are highly similar. In molecular dynamics (MD) calculations, only the defluorinating enzymes sample more compact conformations, which in turn allow more effective interactions with the small fluorine atom. Structural constraints, based on X-ray structures and MD calculations, correctly predict the defluorination activity of the homologous enzyme ST2570.

KW - Amino Acid Sequence

KW - Crystallography, X-Ray

KW - Halogenation

KW - Hydrolases/chemistry

KW - Molecular Dynamics Simulation

KW - Protein Conformation

KW - Sequence Alignment

U2 - 10.1002/cbic.202100414

DO - 10.1002/cbic.202100414

M3 - Article

C2 - 34643018

VL - 23

JO - ChemBioChem

JF - ChemBioChem

SN - 1439-7633

IS - 1

M1 - e202100414

ER -