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Title: Structure of Methylobacterium extorquens malyl-CoA lyase: CoA-substrate binding correlates with domain shift

Abstract

Malyl-CoA lyase (MCL) is an Mg 2+-dependent enzyme that catalyzes the reversible cleavage of (2 S)-4-malyl-CoA to yield acetyl-CoA and glyoxylate. MCL enzymes, which are found in a variety of bacteria, are members of the citrate lyase-like family and are involved in the assimilation of one- and two-carbon compounds. Here, the 1.56 Å resolution X-ray crystal structure of MCL from Methylobacterium extorquens AM1 with bound Mg 2+is presented. Structural alignment with the closely related Rhodobacter sphaeroides malyl-CoA lyase complexed with Mg 2+, oxalate and CoA allows a detailed analysis of the domain motion of the enzyme caused by substrate binding. Alignment of the structures shows that a simple hinge motion centered on the conserved residues Phe268 and Thr269 moves the C-terminal domain by about 30° relative to the rest of the molecule. Furthermore, this domain motion positions a conserved aspartate residue located in the C-terminal domain in the active site of the adjacent monomer, which may serve as a general acid/base in the catalytic mechanism.

Authors:
 [1]; ORCiD logo [2]; ORCiD logo [2];  [2]
  1. Los Alamos National Lab. (LANL), Los Alamos, NM (United States); Univ. Nacional de Santiago del Estero, Santiago del Estero (Argentina)
  2. Los Alamos National Lab. (LANL), Los Alamos, NM (United States)
Publication Date:
Research Org.:
Los Alamos National Lab. (LANL), Los Alamos, NM (United States)
Sponsoring Org.:
USDOE Laboratory Directed Research and Development (LDRD) Program
OSTI Identifier:
1342868
Report Number(s):
LA-UR-16-29566
Journal ID: ISSN 2053-230X; ACSFEN; TRN: US1700925
Grant/Contract Number:  
AC52-06NA25396
Resource Type:
Accepted Manuscript
Journal Name:
Acta Crystallographica. Section F, Structural Biology Communications
Additional Journal Information:
Journal Volume: 73; Journal Issue: 2; Journal ID: ISSN 2053-230X
Publisher:
International Union of Crystallography
Country of Publication:
United States
Language:
English
Subject:
59 BASIC BIOLOGICAL SCIENCES; Biological Science

Citation Formats

Gonzalez, Javier M., Marti-Arbona, Ricardo, Chen, Julian C. -H., and Unkefer, Clifford Jay. Structure of Methylobacterium extorquens malyl-CoA lyase: CoA-substrate binding correlates with domain shift. United States: N. p., 2017. Web. doi:10.1107/S2053230X17001029.
Gonzalez, Javier M., Marti-Arbona, Ricardo, Chen, Julian C. -H., & Unkefer, Clifford Jay. Structure of Methylobacterium extorquens malyl-CoA lyase: CoA-substrate binding correlates with domain shift. United States. doi:10.1107/S2053230X17001029.
Gonzalez, Javier M., Marti-Arbona, Ricardo, Chen, Julian C. -H., and Unkefer, Clifford Jay. Fri . "Structure of Methylobacterium extorquens malyl-CoA lyase: CoA-substrate binding correlates with domain shift". United States. doi:10.1107/S2053230X17001029. https://www.osti.gov/servlets/purl/1342868.
@article{osti_1342868,
title = {Structure of Methylobacterium extorquens malyl-CoA lyase: CoA-substrate binding correlates with domain shift},
author = {Gonzalez, Javier M. and Marti-Arbona, Ricardo and Chen, Julian C. -H. and Unkefer, Clifford Jay},
abstractNote = {Malyl-CoA lyase (MCL) is an Mg2+-dependent enzyme that catalyzes the reversible cleavage of (2S)-4-malyl-CoA to yield acetyl-CoA and glyoxylate. MCL enzymes, which are found in a variety of bacteria, are members of the citrate lyase-like family and are involved in the assimilation of one- and two-carbon compounds. Here, the 1.56 Å resolution X-ray crystal structure of MCL from Methylobacterium extorquens AM1 with bound Mg2+is presented. Structural alignment with the closely related Rhodobacter sphaeroides malyl-CoA lyase complexed with Mg2+, oxalate and CoA allows a detailed analysis of the domain motion of the enzyme caused by substrate binding. Alignment of the structures shows that a simple hinge motion centered on the conserved residues Phe268 and Thr269 moves the C-terminal domain by about 30° relative to the rest of the molecule. Furthermore, this domain motion positions a conserved aspartate residue located in the C-terminal domain in the active site of the adjacent monomer, which may serve as a general acid/base in the catalytic mechanism.},
doi = {10.1107/S2053230X17001029},
journal = {Acta Crystallographica. Section F, Structural Biology Communications},
number = 2,
volume = 73,
place = {United States},
year = {2017},
month = {1}
}

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