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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 50 phosphate) PLP-dependent methionine γ-lyase involved in the biosynthesis of calicheamicins. Here, 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.

Authors:
 [1];  [2];  [1];  [2];  [3];  [2];  [2];  [4];  [2];  [5];  [6];  [5];  [1]
  1. Rice Univ., Houston, TX (United States). Biosciences at Rice
  2. Argonne National Lab. (ANL), Argonne, IL (United States). Biosciences Division and Midwest Center for Structural Genomics
  3. Rice Univ., Houston, TX (United States). Biosciences at Rice; Jaypee Univ. of Information Technology, Waknaghat (India). Dept. of Biotechnology and Bioinformatics
  4. Univ. of Wisconsin, Madison, WI (United States). Dept. of Biochemistry
  5. Univ. of Kentucky, Lexington, KY (United States). Dept. of Pharmaceutical Sciences and College of Pharmacy
  6. Univ. of Kentucky, Lexington, KY (United States). Dept. of Pharmaceutical Sciences and College of Pharmacy; Univ. of Oklahoma, Norman, OK (United States). Dept. of Chemistry and Biochemistry
Publication Date:
Research Org.:
Argonne National Lab. (ANL), Argonne, IL (United States). Advanced Photon Source (APS)
Sponsoring Org.:
USDOE Office of Science (SC), Biological and Environmental Research (BER) (SC-23); National Institutes of Health (NIH); National Center for Advancing Translational Sciences (NCATS)
OSTI Identifier:
1439871
Grant/Contract Number:  
AC02-06CH11357; CA84374; U01GM098248; GM094585; UL1TR000117
Resource Type:
Journal Article: Accepted Manuscript
Journal Name:
Structural Dynamics
Additional Journal Information:
Journal Volume: 3; Journal Issue: 3; Journal ID: ISSN 2329-7778
Publisher:
American Crystallographic Association/AIP
Country of Publication:
United States
Language:
English
Subject:
59 BASIC BIOLOGICAL SCIENCES; 37 INORGANIC, ORGANIC, PHYSICAL, AND ANALYTICAL CHEMISTRY; Enzymes; Conformational dynamics; Crystal structure; Normal modes; Elasticity; Catalysis; Data analysis; Acids; Computer modeling

Citation Formats

Cao, Hongnan, Tan, Kemin, Wang, Fengbin, Bigelow, Lance, Yennamalli, Ragothaman M., Jedrzejczak, Robert, Babnigg, Gyorgy, Bingman, Craig A., Joachimiak, Andrzej, Kharel, Madan K., Singh, Shanteri, Thorson, Jon S., and Phillips, George N.. Structural dynamics of a methionine γ-lyase for calicheamicin biosynthesis: Rotation of the conserved tyrosine stacking with pyridoxal phosphate. United States: N. p., 2016. Web. doi:10.1063/1.4948539.
Cao, Hongnan, Tan, Kemin, Wang, Fengbin, Bigelow, Lance, Yennamalli, Ragothaman M., Jedrzejczak, Robert, Babnigg, Gyorgy, Bingman, Craig A., Joachimiak, Andrzej, Kharel, Madan K., Singh, Shanteri, Thorson, Jon S., & Phillips, George N.. Structural dynamics of a methionine γ-lyase for calicheamicin biosynthesis: Rotation of the conserved tyrosine stacking with pyridoxal phosphate. United States. doi:10.1063/1.4948539.
Cao, Hongnan, Tan, Kemin, Wang, Fengbin, Bigelow, Lance, Yennamalli, Ragothaman M., Jedrzejczak, Robert, Babnigg, Gyorgy, Bingman, Craig A., Joachimiak, Andrzej, Kharel, Madan K., Singh, Shanteri, Thorson, Jon S., and Phillips, George N.. Fri . "Structural dynamics of a methionine γ-lyase for calicheamicin biosynthesis: Rotation of the conserved tyrosine stacking with pyridoxal phosphate". United States. doi:10.1063/1.4948539. https://www.osti.gov/servlets/purl/1439871.
@article{osti_1439871,
title = {Structural dynamics of a methionine γ-lyase for calicheamicin biosynthesis: Rotation of the conserved tyrosine stacking with pyridoxal phosphate},
author = {Cao, Hongnan and Tan, Kemin and Wang, Fengbin and Bigelow, Lance and Yennamalli, Ragothaman M. and Jedrzejczak, Robert and Babnigg, Gyorgy and Bingman, Craig A. and Joachimiak, Andrzej and Kharel, Madan K. and Singh, Shanteri and Thorson, Jon S. and Phillips, George N.},
abstractNote = {CalE6 from Micromonospora echinospora is a (pyridoxal 50 phosphate) PLP-dependent methionine γ-lyase involved in the biosynthesis of calicheamicins. Here, 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.},
doi = {10.1063/1.4948539},
journal = {Structural Dynamics},
number = 3,
volume = 3,
place = {United States},
year = {Fri Apr 29 00:00:00 EDT 2016},
month = {Fri Apr 29 00:00:00 EDT 2016}
}

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