The control of the activity of HIV-1 protease by allosteric regulation of the efficiency of a putative inhibitor by Zn(II) ions was studied. The metal-binding template employed was tris(2-aminoethyl)amine to which to cross-link two peptides through a rigid aromatic spacer. The results showed that the activity of a dimerization inhibitor of HIV-1 protease derived from cross-linked interfacial peptides could be enhanced by controlling the conformation of their connecting unit through Zn(II) complexation. This provides a straightforward example of allosteric regulation of the activity of a synthetic inhibitor by a metal ion, and demonstrates that although Zn(II)-binding process occurs at a remote position, it amplifies the chemical information present in the system, i.e., its ability to recognize a monomer of HIV-1 protease.
Allosteric regulation of a HIV-1 protease inhibitor by Zn(II) ions
GOBBO M;
2001
Abstract
The control of the activity of HIV-1 protease by allosteric regulation of the efficiency of a putative inhibitor by Zn(II) ions was studied. The metal-binding template employed was tris(2-aminoethyl)amine to which to cross-link two peptides through a rigid aromatic spacer. The results showed that the activity of a dimerization inhibitor of HIV-1 protease derived from cross-linked interfacial peptides could be enhanced by controlling the conformation of their connecting unit through Zn(II) complexation. This provides a straightforward example of allosteric regulation of the activity of a synthetic inhibitor by a metal ion, and demonstrates that although Zn(II)-binding process occurs at a remote position, it amplifies the chemical information present in the system, i.e., its ability to recognize a monomer of HIV-1 protease.I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.
