| http://purl.uniprot.org/citations/15713084 | http://www.w3.org/1999/02/22-rdf-syntax-ns#type | http://purl.uniprot.org/core/Journal_Citation |
| http://purl.uniprot.org/citations/15713084 | http://www.w3.org/2000/01/rdf-schema#comment | "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."xsd:string |
| http://purl.uniprot.org/citations/15713084 | http://purl.org/dc/terms/identifier | "doi:10.1021/ja0431307"xsd:string |
| http://purl.uniprot.org/citations/15713084 | http://purl.uniprot.org/core/author | "Urbauer J.L."xsd:string |
| http://purl.uniprot.org/citations/15713084 | http://purl.uniprot.org/core/author | "Yang W."xsd:string |
| http://purl.uniprot.org/citations/15713084 | http://purl.uniprot.org/core/author | "Yang J.J."xsd:string |
| http://purl.uniprot.org/citations/15713084 | http://purl.uniprot.org/core/author | "Ye Y."xsd:string |
| http://purl.uniprot.org/citations/15713084 | http://purl.uniprot.org/core/author | "Kearney A."xsd:string |
| http://purl.uniprot.org/citations/15713084 | http://purl.uniprot.org/core/author | "Hellinga H.W."xsd:string |
| http://purl.uniprot.org/citations/15713084 | http://purl.uniprot.org/core/author | "van der Merwe P.A."xsd:string |
| http://purl.uniprot.org/citations/15713084 | http://purl.uniprot.org/core/author | "Li S.Y."xsd:string |
| http://purl.uniprot.org/citations/15713084 | http://purl.uniprot.org/core/author | "Liu Z.R."xsd:string |
| http://purl.uniprot.org/citations/15713084 | http://purl.uniprot.org/core/author | "Wilkins A.L."xsd:string |
| http://purl.uniprot.org/citations/15713084 | http://purl.uniprot.org/core/date | "2005"xsd:gYear |
| http://purl.uniprot.org/citations/15713084 | http://purl.uniprot.org/core/name | "J Am Chem Soc"xsd:string |
| http://purl.uniprot.org/citations/15713084 | http://purl.uniprot.org/core/pages | "2085-2093"xsd:string |
| http://purl.uniprot.org/citations/15713084 | http://purl.uniprot.org/core/title | "Design of a calcium-binding protein with desired structure in a cell adhesion molecule."xsd:string |
| http://purl.uniprot.org/citations/15713084 | http://purl.uniprot.org/core/volume | "127"xsd:string |
| http://purl.uniprot.org/citations/15713084 | http://www.w3.org/2004/02/skos/core#exactMatch | http://purl.uniprot.org/pubmed/15713084 |
| http://purl.uniprot.org/citations/15713084 | http://xmlns.com/foaf/0.1/primaryTopicOf | https://pubmed.ncbi.nlm.nih.gov/15713084 |
| http://purl.uniprot.org/uniprot/#_P08921-mappedCitation-15713084 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/15713084 |
| http://purl.uniprot.org/uniprot/P08921 | http://purl.uniprot.org/core/mappedCitation | http://purl.uniprot.org/citations/15713084 |