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Theoretical study of the conformation of the lipoamide arm in a mutant H protein

Theoretical study of the conformation of the lipoamide arm in a mutant H protein The lipoamide arm of the H protein plays a pivotal role in the catalytic cycle of the glycine decarboxylase complex (GDC) by being successively methylamine loaded (Hmet), reduced (Hred), and oxidized (Hox). In a previous study, we calculated free‐energy surfaces as a function of the lipoamide arm position of the three forms of the wild‐type protein and found close agreement with the available experimental data. Our simulations, together with crystallographic and NMR data, showed that the methylamine‐loaded arm is locked in a cavity by interaction with Ser12, Glu14, and Asp67. In this work, we investigate the behavior of the methylamine‐loaded form of a mutant H protein (HEA) where Glu14 has been replaced by Ala. We find that the arm can still be held in the cavity but that the energy barrier to release of the arm is halved from ∼40 kcal mol−1 for Hmet to ∼12 kcal mol−1 for HEA. To compensate for the loss of Glu14, the methylamine group shifts toward Ser66 in the mutant form. These results provide a structural basis for the equilibrium between the loaded and the unloaded forms of the arm observed by Gueguen et al. (Gueguen et al., J Biol Chem 1999;274:26344–26352) in HEA. Proteins 2001;45:237–240. © 2001 Wiley‐Liss, Inc. http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png Proteins: Structure Function and Bioinformatics Wiley

Theoretical study of the conformation of the lipoamide arm in a mutant H protein

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References (13)

Publisher
Wiley
Copyright
Copyright © 2001 Wiley Subscription Services
ISSN
0887-3585
eISSN
1097-0134
DOI
10.1002/prot.1144
Publisher site
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Abstract

The lipoamide arm of the H protein plays a pivotal role in the catalytic cycle of the glycine decarboxylase complex (GDC) by being successively methylamine loaded (Hmet), reduced (Hred), and oxidized (Hox). In a previous study, we calculated free‐energy surfaces as a function of the lipoamide arm position of the three forms of the wild‐type protein and found close agreement with the available experimental data. Our simulations, together with crystallographic and NMR data, showed that the methylamine‐loaded arm is locked in a cavity by interaction with Ser12, Glu14, and Asp67. In this work, we investigate the behavior of the methylamine‐loaded form of a mutant H protein (HEA) where Glu14 has been replaced by Ala. We find that the arm can still be held in the cavity but that the energy barrier to release of the arm is halved from ∼40 kcal mol−1 for Hmet to ∼12 kcal mol−1 for HEA. To compensate for the loss of Glu14, the methylamine group shifts toward Ser66 in the mutant form. These results provide a structural basis for the equilibrium between the loaded and the unloaded forms of the arm observed by Gueguen et al. (Gueguen et al., J Biol Chem 1999;274:26344–26352) in HEA. Proteins 2001;45:237–240. © 2001 Wiley‐Liss, Inc.

Journal

Proteins: Structure Function and Bioinformatics – Wiley

Published: Jan 15, 2001

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