1yik
From Proteopedia
(New page: 200px<br /> <applet load="1yik" size="450" color="white" frame="true" align="right" spinBox="true" caption="1yik, resolution 1.75Å" /> '''Structure of Hen eg...) |
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| - | [[Image:1yik.gif|left|200px]]<br /> | + | [[Image:1yik.gif|left|200px]]<br /><applet load="1yik" size="350" color="white" frame="true" align="right" spinBox="true" |
| - | <applet load="1yik" size=" | + | |
caption="1yik, resolution 1.75Å" /> | caption="1yik, resolution 1.75Å" /> | ||
'''Structure of Hen egg white lysozyme soaked with Cu-cyclam'''<br /> | '''Structure of Hen egg white lysozyme soaked with Cu-cyclam'''<br /> | ||
==Overview== | ==Overview== | ||
| - | The macrocyclic antiviral drug xylyl-bicyclam blocks entry of HIV into | + | 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== | ==About this Structure== | ||
| - | 1YIK is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Gallus_gallus Gallus gallus] with CL, NA, ACT and MM1 as [http://en.wikipedia.org/wiki/ligands ligands]. Active as [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] Full crystallographic information is available from [http:// | + | 1YIK is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Gallus_gallus Gallus gallus] with <scene name='pdbligand=CL:'>CL</scene>, <scene name='pdbligand=NA:'>NA</scene>, <scene name='pdbligand=ACT:'>ACT</scene> and <scene name='pdbligand=MM1:'>MM1</scene> as [http://en.wikipedia.org/wiki/ligands ligands]. Active as [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] Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1YIK OCA]. |
==Reference== | ==Reference== | ||
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[[Category: Single protein]] | [[Category: Single protein]] | ||
[[Category: Bella, J.]] | [[Category: Bella, J.]] | ||
| - | [[Category: Hunter, T | + | [[Category: Hunter, T M.]] |
[[Category: Liang, X.]] | [[Category: Liang, X.]] | ||
| - | [[Category: McNae, I | + | [[Category: McNae, I W.]] |
[[Category: Parsons, S.]] | [[Category: Parsons, S.]] | ||
| - | [[Category: Sadler, P | + | [[Category: Sadler, P J.]] |
| - | [[Category: Walkinshaw, M | + | [[Category: Walkinshaw, M D.]] |
[[Category: ACT]] | [[Category: ACT]] | ||
[[Category: CL]] | [[Category: CL]] | ||
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[[Category: hydrolase]] | [[Category: hydrolase]] | ||
| - | ''Page seeded by [http:// | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 16:05:40 2008'' |
Revision as of 14:05, 21 February 2008
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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 , , and 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
Page seeded by OCA on Thu Feb 21 16:05:40 2008
Categories: Gallus gallus | Lysozyme | Single protein | Bella, J. | Hunter, T M. | Liang, X. | McNae, I W. | Parsons, S. | Sadler, P J. | Walkinshaw, M D. | ACT | CL | MM1 | NA | Hydrolase
