Binding site differences revealed by crystal structures of Plasmodium falciparum and bovine acyl-CoA binding protein

TY - JOUR

T1 - Binding site differences revealed by crystal structures of Plasmodium falciparum and bovine acyl-CoA binding protein

AU - van Aalten, D. M. F.

AU - Milne, K. G.

AU - Zou, J. Y.

AU - Kleywegt, G. J.

AU - Bergfors, T.

AU - Ferguson, Michael A. J.

AU - Knudsen, J.

AU - Jones, T. A.

PY - 2001/5/25

Y1 - 2001/5/25

N2 - Acyl-CoA binding protein (ACBP) maintains a pool of fatty acyl-CoA molecules in the cell and plays a role in fatty acid metabolism. The biochemical properties of Plasmodium falciparum ACBP are described together with the 2.0 Angstrom resolution crystal structures of a P, falciparum ACBP-acyl-CoA complex and of bovine ACBP in two crystal forms. Overall, the bovine ACBP crystal structures are similar to the NMR structures published previously; however, the bovine and parasite ACBP structures are less similar. The parasite ACBP is shown to have a different Ligand-binding pocket, leading to an acyl-CoA binding specificity different from that of bovine ACBP. Several non-conservative differences in residues that interact with the ligand were identified between the mammalian and parasite ACBPs. These, together with measured binding-specificity differences, suggest that there is a potential for the design of molecules that might selectively block the acyl-CoA binding site. (C) 2001 Academic Press.

AB - Acyl-CoA binding protein (ACBP) maintains a pool of fatty acyl-CoA molecules in the cell and plays a role in fatty acid metabolism. The biochemical properties of Plasmodium falciparum ACBP are described together with the 2.0 Angstrom resolution crystal structures of a P, falciparum ACBP-acyl-CoA complex and of bovine ACBP in two crystal forms. Overall, the bovine ACBP crystal structures are similar to the NMR structures published previously; however, the bovine and parasite ACBP structures are less similar. The parasite ACBP is shown to have a different Ligand-binding pocket, leading to an acyl-CoA binding specificity different from that of bovine ACBP. Several non-conservative differences in residues that interact with the ligand were identified between the mammalian and parasite ACBPs. These, together with measured binding-specificity differences, suggest that there is a potential for the design of molecules that might selectively block the acyl-CoA binding site. (C) 2001 Academic Press.

U2 - 10.1006/jmbi.2001.4749

DO - 10.1006/jmbi.2001.4749

M3 - Article

C2 - 11491287

SN - 0022-2836

VL - 309

SP - 181

EP - 192

JO - Journal of Molecular Biology

JF - Journal of Molecular Biology

IS - 1

ER -