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1t6w

From Proteopedia

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[[Image:1t6w.gif|left|200px]]
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{{STRUCTURE_1t6w| PDB=1t6w | SCENE= }}
{{STRUCTURE_1t6w| PDB=1t6w | SCENE= }}
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'''RATIONAL DESIGN OF A CALCIUM-BINDING ADHESION PROTEIN NMR, 20 STRUCTURES'''
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===RATIONAL DESIGN OF A CALCIUM-BINDING ADHESION PROTEIN NMR, 20 STRUCTURES===
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==Overview==
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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.
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{{ABSTRACT_PUBMED_15713084}}
==About this Structure==
==About this Structure==
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1T6W is a [[Single protein]] structure of sequence from [http://en.wikipedia.org/wiki/Rattus_norvegicus Rattus norvegicus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1T6W OCA].
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1T6W is a [[Single protein]] structure of sequence from [http://en.wikipedia.org/wiki/Rattus_norvegicus Rattus norvegicus]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1T6W OCA].
==Reference==
==Reference==
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[[Category: Design]]
[[Category: Design]]
[[Category: Nmr]]
[[Category: Nmr]]
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sat May 3 09:36:26 2008''
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Tue Jul 29 02:43:29 2008''

Revision as of 23:43, 28 July 2008

Image:1t6w.png

Template:STRUCTURE 1t6w

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

Template:ABSTRACT PUBMED 15713084

About this Structure

1T6W is a Single protein structure of sequence from Rattus norvegicus. Full experimental 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

Page seeded by OCA on Tue Jul 29 02:43:29 2008

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