1t6w

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|PDB= 1t6w |SIZE=350|CAPTION= <scene name='initialview01'>1t6w</scene>
|PDB= 1t6w |SIZE=350|CAPTION= <scene name='initialview01'>1t6w</scene>
|SITE=
|SITE=
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|LIGAND= <scene name='pdbligand=CA:CALCIUM ION'>CA</scene>
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|LIGAND= <scene name='pdbligand=CA:CALCIUM+ION'>CA</scene>
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|ACTIVITY=
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|RELATEDENTRY=
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|RESOURCES=<span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1t6w FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1t6w OCA], [http://www.ebi.ac.uk/pdbsum/1t6w PDBsum], [http://www.rcsb.org/pdb/explore.do?structureId=1t6w RCSB]</span>
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[[Category: Yang, W.]]
[[Category: Yang, W.]]
[[Category: Ye, Y.]]
[[Category: Ye, Y.]]
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[[Category: CA]]
 
[[Category: calcium-binding protein]]
[[Category: calcium-binding protein]]
[[Category: cd2]]
[[Category: cd2]]
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[[Category: nmr]]
[[Category: nmr]]
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Mar 20 14:14:39 2008''
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sun Mar 30 23:52:09 2008''

Revision as of 20:52, 30 March 2008


PDB ID 1t6w

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Ligands:
Resources: FirstGlance, OCA, PDBsum, RCSB
Coordinates: save as pdb, mmCIF, xml



RATIONAL DESIGN OF A CALCIUM-BINDING ADHESION PROTEIN NMR, 20 STRUCTURES


Overview

Ca2+, "a signal of life and death", controls numerous cellular processes through interactions with proteins. An effective approach to understanding the role of Ca2+ is the design of a Ca2+-binding protein with predicted structural and functional properties. To design de novo Ca2+-binding sites in proteins is challenging due to the high coordination numbers and the incorporation of charged ligand residues, in addition to Ca2+-induced conformational change. Here, we demonstrate the successful design of a Ca2+-binding site in the non-Ca2+-binding cell adhesion protein CD2. This designed protein, Ca.CD2, exhibits selectivity for Ca2+ versus other di- and monovalent cations. In addition, La3+ (Kd 5.0 microM) and Tb3+ (Kd 6.6 microM) bind to the designed protein somewhat more tightly than does Ca2+ (Kd 1.4 mM). More interestingly, Ca.CD2 retains the native ability to associate with the natural target molecule. The solution structure reveals that Ca.CD2 binds Ca2+ at the intended site with the designed arrangement, which validates our general strategy for designing de novo Ca2+-binding proteins. The structural information also provides a close view of structural determinants that are necessary for a functional protein to accommodate the metal-binding site. This first success in designing Ca2+-binding proteins with desired structural and functional properties opens a new avenue in unveiling key determinants to Ca2+ binding, the mechanism of Ca2+ signaling, and Ca2+-dependent cell adhesion, while avoiding the complexities of the global conformational changes and cooperativity in natural Ca2+-binding proteins. It also represents a major achievement toward designing functional proteins controlled by Ca2+ binding.

About this Structure

1T6W is a Single protein structure of sequence from Rattus norvegicus. Full crystallographic information is available from OCA.

Reference

Design of a calcium-binding protein with desired structure in a cell adhesion molecule., Yang W, Wilkins AL, Ye Y, Liu ZR, Li SY, Urbauer JL, Hellinga HW, Kearney A, van der Merwe PA, Yang JJ, J Am Chem Soc. 2005 Feb 23;127(7):2085-93. PMID:15713084

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