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Title: Conformational changes on substrate binding revealed by structures of Methylobacterium extorquens malate dehydrogenase

Abstract

In this paper, three high-resolution X-ray crystal structures of malate dehydrogenase (MDH; EC 1.1.1.37) from the methylotrophMethylobacterium extorquensAM1 are presented. By comparing the structures of apo MDH, a binary complex of MDH and NAD +, and a ternary complex of MDH and oxaloacetate with ADP-ribose occupying the pyridine nucleotide-binding site, conformational changes associated with the formation of the catalytic complex were characterized. While the substrate-binding site is accessible in the enzyme resting state or NAD +-bound forms, the substrate-bound form exhibits a closed conformation. This conformational change involves the transition of an α-helix to a 3 10-helix, which causes the adjacent loop to close the active site following coenzyme and substrate binding. Finally, in the ternary complex, His284 forms a hydrogen bond to the C2 carbonyl of oxaloacetate, placing it in a position to donate a proton in the formation of (2S)-malate.

Authors:
ORCiD logo [1]; ORCiD logo [2]; ORCiD logo [2];  [2]; ORCiD logo [2]
  1. Universidad Nacional de Santiago del Estero (Argentina); Los Alamos National Lab. (LANL), Los Alamos, NM (United States)
  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:
1477666
Report Number(s):
LA-UR-18-24857
Journal ID: ISSN 2053-230X; ACSFEN
Grant/Contract Number:  
AC52-06NA25396
Resource Type:
Accepted Manuscript
Journal Name:
Acta Crystallographica. Section F, Structural Biology Communications
Additional Journal Information:
Journal Volume: 74; Journal Issue: 10; 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

González, Javier M., Marti-Arbona, Ricardo, Chen, Julian C., Broom-Peltz, Brian, and Unkefer, Clifford Jay. Conformational changes on substrate binding revealed by structures of Methylobacterium extorquens malate dehydrogenase. United States: N. p., 2018. Web. doi:10.1107/S2053230X18011809.
González, Javier M., Marti-Arbona, Ricardo, Chen, Julian C., Broom-Peltz, Brian, & Unkefer, Clifford Jay. Conformational changes on substrate binding revealed by structures of Methylobacterium extorquens malate dehydrogenase. United States. doi:10.1107/S2053230X18011809.
González, Javier M., Marti-Arbona, Ricardo, Chen, Julian C., Broom-Peltz, Brian, and Unkefer, Clifford Jay. Wed . "Conformational changes on substrate binding revealed by structures of Methylobacterium extorquens malate dehydrogenase". United States. doi:10.1107/S2053230X18011809. https://www.osti.gov/servlets/purl/1477666.
@article{osti_1477666,
title = {Conformational changes on substrate binding revealed by structures of Methylobacterium extorquens malate dehydrogenase},
author = {González, Javier M. and Marti-Arbona, Ricardo and Chen, Julian C. and Broom-Peltz, Brian and Unkefer, Clifford Jay},
abstractNote = {In this paper, three high-resolution X-ray crystal structures of malate dehydrogenase (MDH; EC 1.1.1.37) from the methylotrophMethylobacterium extorquensAM1 are presented. By comparing the structures of apo MDH, a binary complex of MDH and NAD+, and a ternary complex of MDH and oxaloacetate with ADP-ribose occupying the pyridine nucleotide-binding site, conformational changes associated with the formation of the catalytic complex were characterized. While the substrate-binding site is accessible in the enzyme resting state or NAD+-bound forms, the substrate-bound form exhibits a closed conformation. This conformational change involves the transition of an α-helix to a 310-helix, which causes the adjacent loop to close the active site following coenzyme and substrate binding. Finally, in the ternary complex, His284 forms a hydrogen bond to the C2 carbonyl of oxaloacetate, placing it in a position to donate a proton in the formation of (2S)-malate.},
doi = {10.1107/S2053230X18011809},
journal = {Acta Crystallographica. Section F, Structural Biology Communications},
number = 10,
volume = 74,
place = {United States},
year = {2018},
month = {9}
}

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