10
T.M.A. Franco et al. / Archives of Biochemistry and Biophysics 517 (2012) 1–11
domain that eliminates the need for dimerization. The residues
Arg509, Val510, Tyr512, Asp513, and Thr521, which form intermo-
lecular hydrogen bonds, are conserved in P. horikoshii and E. coli
(Fig. 7). These residues are also conserved in M. tuberculosis and hu-
mans with the exception of Val510 (Ile in humans) and Leu512 in
M. tuberculosis, which are obviously not involved in dimerization in
the crystal (PDB ID: 2VXO) of monomeric human GMPS [14]. The
dimerization domain is adjacent to the ATP-binding site of the
ATPPase domain. Contacts between the domains are highly con-
served, including the proline- and glycine-rich linker peptide (res-
idues 403–408), which in E. coli (PDB ID: 1GPM) is anchored in the
dimerization domain by the specific contacts of invariant residues
[36]. On the other hand, all residues of the putative XMP-recogniz-
ing amino acid residues are conserved between the polypeptide
sequences included in the alignment (Fig. 7). MtGMPS has fairly
high identity to prokaryotic GMPSs (M. tuberculosis and E. coli
GMPSs: 47.39%; M. tuberculosis and P. horikoshii GMPSs: 31.81%),
and relatively low identity to the human protein (M. tuberculosis
and human GMPSs: 15.50%).
Research Council of Brazil (CNPq). T.M.A.F., D.C.R., R.G.D., and
D.M.L. acknowledge scholarships awarded by CNPq.
Appendix A. Supplementary data
Supplementary data associated with this article can be found, in
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Acknowledgments
This work was supported by funds of Decit/SCTIE/MS-MCT-
CNPq-FNDCT-CAPES to National Institute of Science and Technol-
ogy on Tuberculosis (INCT-TB) to D.S.S. and L.A.B. L.A.B. and D.S.S.
also acknowledge financial support awarded by FAPERGS-CNPq-
PRONEX-2009. D.S.S. (CNPq, 304051/1975-06) and L.A.B. (CNPq,
520182/99-5) and are Research Career Awardees of the National