1yik

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spinqualitylabelsall models 1yik, resolution 1.75Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image

Structure of Hen egg white lysozyme soaked with Cu-cyclam

Overview

The macrocyclic antiviral drug xylyl-bicyclam blocks entry of HIV into, cells by targeting the CXCR4 coreceptor, a seven-helix transmembrane, G-protein-coupled receptor. Its affinity for CXCR4 is enhanced by binding, to Cu2+, Ni2+, or Zn2+. Metallocyclams have a rich configurational, chemistry and proteins may bind selectively to specific metallocyclam, configurations. Our studies of lysozyme reveal structural details of, protein-metallocyclam interactions that are important for receptor, recognition. Solution NMR studies show that Cu-cyclam interacts with, specific tryptophan residues of lysozyme (Trp-62, Trp-63, and Trp-123)., Two major binding sites for both Cu-cyclam and Cu2-xylyl-bicyclam were, detected by x-ray crystallography. In the first site, Cu2+ in one cyclam, ring of Cu2-xylyl-bicyclam adopts a trans configuration and is coordinated, to a carboxylate oxygen of Asp-101, whereas for Cu-cyclam two ring NH, groups form H bonds to the carboxylate oxygens of Asp-101, stabilizing an, unusual cis (folded) cyclam configuration. For both complexes in this, site, a cyclam ring is sandwiched between the indole side chains of two, tryptophan residues (Trp-62 and Trp-63). In the second site, a trans, cyclam ring is stacked on Trp-123 and H bonded to the backbone carbonyl of, Gly-117. We show that there is a pocket in a model of the human CXCR4, coreceptor in which trans and cis configurations of metallobicyclam can, bind by direct metal coordination to carboxylate side chains, cyclam-NH...carboxylate H bonding, together with hydrophobic interactions, with tryptophan residues. These studies provide a structural basis for the, design of macrocycles that bind stereospecifically to G-coupled and other, protein receptors.

About this Structure

1YIK is a Single protein structure of sequence from Gallus gallus with CL, NA, ACT and MM1 as ligands. Active as Lysozyme, with EC number 3.2.1.17 Full crystallographic information is available from OCA.

Reference

Protein recognition of macrocycles: binding of anti-HIV metallocyclams to lysozyme., Hunter TM, McNae IW, Liang X, Bella J, Parsons S, Walkinshaw MD, Sadler PJ, Proc Natl Acad Sci U S A. 2005 Feb 15;102(7):2288-92. Epub 2005 Feb 8. PMID:15701702

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