Structural dynamics of a methionine γ-lyase for calicheamicin biosynthesis: Rotation of the conserved tyrosine stacking with pyridoxal phosphate

Hongnan Cao; Kemin Tan; Fengbin Wang; Lance Bigelow; Ragothaman M. Yennamalli; Robert Jedrzejczak; Gyorgy Babnigg; Craig A. Bingman; Andrzej Joachimiak; Madan K. Kharel; Shanteri Singh; Jon S. Thorson; George N. Phillips

doi:10.1063/1.4948539

Structural dynamics of a methionine γ-lyase for calicheamicin biosynthesis: Rotation of the conserved tyrosine stacking with pyridoxal phosphate

Hongnan Cao, Kemin Tan, Fengbin Wang, Lance Bigelow, Ragothaman M. Yennamalli, Robert Jedrzejczak, Gyorgy Babnigg, Craig A. Bingman, Andrzej Joachimiak, Madan K. Kharel, Shanteri Singh, Jon S. Thorson, George N. Phillips

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

3 Scopus citations

Abstract

CalE6 from Micromonospora echinospora is a (pyridoxal 5' phosphate) PLP-dependent methionine γ-lyase involved in the biosynthesis of calicheamicins. We report the crystal structure of a CalE6 2-(N-morpholino)ethanesulfonic acid complex showing ligand-induced rotation of Tyr100, which stacks with PLP, resembling the corresponding tyrosine rotation of true catalytic intermediates of CalE6 homologs. Elastic network modeling and crystallographic ensemble refinement reveal mobility of the N-terminal loop, which involves both tetrameric assembly and PLP binding. Modeling and comparative structural analysis of PLP-dependent enzymes involved in Cys/Met metabolism shine light on the functional implications of the intrinsic dynamic properties of CalE6 in catalysis and holoenzyme maturation.

Original language	English
Article number	034702
Journal	Structural Dynamics
Volume	3
Issue number	3
DOIs	https://doi.org/10.1063/1.4948539
State	Published - May 1 2016

Bibliographical note

Publisher Copyright:
© 2016 Author(s).

Funding

This work was supported by the National Institutes of Health Grant Nos. CA84374 (J.S.T.), U01GM098248 (G.N.P.), and GM094585 (A.J.) and the National Center for Advancing Translational Sciences (UL1TR000117). Results shown in this report are derived from work performed at 19-ID beamline of Argonne National Laboratory, Structural Biology Center at the Advanced Photon Source. Argonne is operated by UChicago Argonne, LLC, for the U.S. Department of Energy, Office of Biological and Environmental Research under Contract No. DEAC02-06CH11357.

Funders	Funder number
National Institutes of Health (NIH)	U01GM098248, GM094585, CA84374
Michigan State University-U.S. Department of Energy (MSU-DOE) Plant Research Laboratory
National Center for Advancing Translational Sciences (NCATS)	UL1TR000117
Biological and Environmental Research	DEAC02-06CH11357
Argonne National Laboratory

ASJC Scopus subject areas

Radiation
Instrumentation
Condensed Matter Physics
Spectroscopy

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Cao, H., Tan, K., Wang, F., Bigelow, L., Yennamalli, R. M., Jedrzejczak, R., Babnigg, G., Bingman, C. A., Joachimiak, A., Kharel, M. K., Singh, S., Thorson, J. S., & Phillips, G. N. (2016). Structural dynamics of a methionine γ-lyase for calicheamicin biosynthesis: Rotation of the conserved tyrosine stacking with pyridoxal phosphate. Structural Dynamics, 3(3), Article 034702. https://doi.org/10.1063/1.4948539

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title = "Structural dynamics of a methionine γ-lyase for calicheamicin biosynthesis: Rotation of the conserved tyrosine stacking with pyridoxal phosphate",

abstract = "CalE6 from Micromonospora echinospora is a (pyridoxal 5' phosphate) PLP-dependent methionine γ-lyase involved in the biosynthesis of calicheamicins. We report the crystal structure of a CalE6 2-(N-morpholino)ethanesulfonic acid complex showing ligand-induced rotation of Tyr100, which stacks with PLP, resembling the corresponding tyrosine rotation of true catalytic intermediates of CalE6 homologs. Elastic network modeling and crystallographic ensemble refinement reveal mobility of the N-terminal loop, which involves both tetrameric assembly and PLP binding. Modeling and comparative structural analysis of PLP-dependent enzymes involved in Cys/Met metabolism shine light on the functional implications of the intrinsic dynamic properties of CalE6 in catalysis and holoenzyme maturation.",

author = "Hongnan Cao and Kemin Tan and Fengbin Wang and Lance Bigelow and Yennamalli, {Ragothaman M.} and Robert Jedrzejczak and Gyorgy Babnigg and Bingman, {Craig A.} and Andrzej Joachimiak and Kharel, {Madan K.} and Shanteri Singh and Thorson, {Jon S.} and Phillips, {George N.}",

note = "Publisher Copyright: {\textcopyright} 2016 Author(s).",

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doi = "10.1063/1.4948539",

language = "English",

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Cao, H, Tan, K, Wang, F, Bigelow, L, Yennamalli, RM, Jedrzejczak, R, Babnigg, G, Bingman, CA, Joachimiak, A, Kharel, MK, Singh, S, Thorson, JS & Phillips, GN 2016, 'Structural dynamics of a methionine γ-lyase for calicheamicin biosynthesis: Rotation of the conserved tyrosine stacking with pyridoxal phosphate', Structural Dynamics, vol. 3, no. 3, 034702. https://doi.org/10.1063/1.4948539

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T1 - Structural dynamics of a methionine γ-lyase for calicheamicin biosynthesis

T2 - Rotation of the conserved tyrosine stacking with pyridoxal phosphate

AU - Cao, Hongnan

AU - Tan, Kemin

AU - Wang, Fengbin

AU - Bigelow, Lance

AU - Yennamalli, Ragothaman M.

AU - Jedrzejczak, Robert

AU - Babnigg, Gyorgy

AU - Bingman, Craig A.

AU - Joachimiak, Andrzej

AU - Kharel, Madan K.

AU - Singh, Shanteri

AU - Thorson, Jon S.

AU - Phillips, George N.

PY - 2016/5/1

Y1 - 2016/5/1

N2 - CalE6 from Micromonospora echinospora is a (pyridoxal 5' phosphate) PLP-dependent methionine γ-lyase involved in the biosynthesis of calicheamicins. We report the crystal structure of a CalE6 2-(N-morpholino)ethanesulfonic acid complex showing ligand-induced rotation of Tyr100, which stacks with PLP, resembling the corresponding tyrosine rotation of true catalytic intermediates of CalE6 homologs. Elastic network modeling and crystallographic ensemble refinement reveal mobility of the N-terminal loop, which involves both tetrameric assembly and PLP binding. Modeling and comparative structural analysis of PLP-dependent enzymes involved in Cys/Met metabolism shine light on the functional implications of the intrinsic dynamic properties of CalE6 in catalysis and holoenzyme maturation.

AB - CalE6 from Micromonospora echinospora is a (pyridoxal 5' phosphate) PLP-dependent methionine γ-lyase involved in the biosynthesis of calicheamicins. We report the crystal structure of a CalE6 2-(N-morpholino)ethanesulfonic acid complex showing ligand-induced rotation of Tyr100, which stacks with PLP, resembling the corresponding tyrosine rotation of true catalytic intermediates of CalE6 homologs. Elastic network modeling and crystallographic ensemble refinement reveal mobility of the N-terminal loop, which involves both tetrameric assembly and PLP binding. Modeling and comparative structural analysis of PLP-dependent enzymes involved in Cys/Met metabolism shine light on the functional implications of the intrinsic dynamic properties of CalE6 in catalysis and holoenzyme maturation.

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Structural dynamics of a methionine γ-lyase for calicheamicin biosynthesis: Rotation of the conserved tyrosine stacking with pyridoxal phosphate

Abstract

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