1yik
From Proteopedia
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|PDB= 1yik |SIZE=350|CAPTION= <scene name='initialview01'>1yik</scene>, resolution 1.75Å | |PDB= 1yik |SIZE=350|CAPTION= <scene name='initialview01'>1yik</scene>, resolution 1.75Å | ||
|SITE= | |SITE= | ||
| - | |LIGAND= <scene name='pdbligand= | + | |LIGAND= <scene name='pdbligand=ACT:ACETATE+ION'>ACT</scene>, <scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=MM1:1,4,8,11-TETRAAZA-CYCLOTETRADECANE+CU(II)'>MM1</scene>, <scene name='pdbligand=NA:SODIUM+ION'>NA</scene> |
| - | |ACTIVITY= [http://en.wikipedia.org/wiki/Lysozyme Lysozyme], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.2.1.17 3.2.1.17] | + | |ACTIVITY= <span class='plainlinks'>[http://en.wikipedia.org/wiki/Lysozyme Lysozyme], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.2.1.17 3.2.1.17] </span> |
|GENE= | |GENE= | ||
| + | |DOMAIN= | ||
| + | |RELATEDENTRY= | ||
| + | |RESOURCES=<span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1yik FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1yik OCA], [http://www.ebi.ac.uk/pdbsum/1yik PDBsum], [http://www.rcsb.org/pdb/explore.do?structureId=1yik RCSB]</span> | ||
}} | }} | ||
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[[Category: Sadler, P J.]] | [[Category: Sadler, P J.]] | ||
[[Category: Walkinshaw, M D.]] | [[Category: Walkinshaw, M D.]] | ||
| - | [[Category: ACT]] | ||
| - | [[Category: CL]] | ||
| - | [[Category: MM1]] | ||
| - | [[Category: NA]] | ||
[[Category: hydrolase]] | [[Category: hydrolase]] | ||
| - | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Mon Mar 31 01:08:38 2008'' |
Revision as of 22:08, 30 March 2008
| |||||||
| , resolution 1.75Å | |||||||
|---|---|---|---|---|---|---|---|
| Ligands: | , , , | ||||||
| Activity: | Lysozyme, with EC number 3.2.1.17 | ||||||
| Resources: | FirstGlance, OCA, PDBsum, RCSB | ||||||
| Coordinates: | save as pdb, mmCIF, xml | ||||||
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. 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
Page seeded by OCA on Mon Mar 31 01:08:38 2008
