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Theoretical study of the conformation of the H‐protein lipoamide arm as a function of its terminal group
Author(s) -
Roche Olivier,
Hinsen Konrad,
Field Martin J.
Publication year - 1999
Publication title -
proteins: structure, function, and bioinformatics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.699
H-Index - 191
eISSN - 1097-0134
pISSN - 0887-3585
DOI - 10.1002/(sici)1097-0134(19990801)36:2<228::aid-prot8>3.0.co;2-q
Subject(s) - crystallography , hox gene , chemistry , group (periodic table) , biochemistry , organic chemistry , transcription factor , gene
The glycine decarboxylase complex consists of four different proteins (the L‐, P‐, H‐, and T‐proteins). The H‐protein plays a central role in communication among the other enzymes, as its lipoamide arm interacts successively with each of the components of the complex. The crystal structures of two states of the H‐protein have been resolved: the oxidized form, H ox at 2 Å and the methylamine‐loaded form, H met at 2.2 Å. However, the position of the arm for the reduced form, H red , is still unknown. We have performed numerical free‐energy calculations in order to better understand the differences in the structures and to elucidate the conformation of the arm in H red . The results of the simulations are in agreement with the crystallographic results, as the minima of the free energy surface for H ox and H met correspond to the crystal structures. For H red , we observe a single minimum in which the arm is on the surface of the H‐protein, close to its position in the H ox structure. In all of our simulations, the lower, lysine portion of the arm remains bound to the protein, which substantially reduces the number of accessible arm configurations. An analysis of the stability of H met in the cavity shows that electrostatic interactions are crucial for locking the arm in the bottom of the cavity, especially near Glu14. In addition, the analysis shows that there is a water molecule, also observed in the crystallographic structure, that binds to the arm's terminal NH 3 + group and helps to fix it in the cavity. In conclusion, because of the close agreement of the results of our calculations with the available experimental evidence, we are able to suggest a structural basis for the observed behavior. Proteins 1999;36: 228–237. © 1999 Wiley‐Liss, Inc.