Einzeltreffer — DigiBib

The invention relates to the human protein FRAP, and in particular to the FKBP12-rapamycin binding domain thereof and to the ternary complex formed by the FRB domain, rapamycin and FKBP12. A new crystalline composition comprising the ternary complex, coordinates defining its three dimensional structure in atomic detail, and uses thereof are disclosed.

Titel:	Crystalline FRAP complex
Autor/in / Beteiligte Person:	Clardy, Jon C. ; Choi, Jungwon
Link:	View record in USPTO Patent Grants (Volltext)
Veröffentlichung:	1999
Medientyp:	Patent
Sonstiges:	Nachgewiesen in: USPTO Patent Grants Sprachen: English Patent Number: 5,939,528 Publication Date: August 17, 1999 Appl. No: 08/963,601 Application Filed: October 31, 1997 Assignees: Cornell Research Foundation, Inc. (Ithaca, NY) Claim: We claim Claim: 1. An orthorhombic crystalline composition in the space group P2.sub.1 2.sub.1 2.sub.1 which diffracts X-rays at a resolution of 2.7 .ANG. or better, each asymmetric unit of which containing one complex comprising Claim: (a) a first protein comprising a peptide sequence derived or selected from the peptide sequence of human FK506 binding protein 12 (FKBP12) Claim: (b) a second protein comprising a peptide sequence derived or selected from the peptide sequence of an FKBP:rapamycin binding domain of human FKBP:Rapamycin Associated Protein (FRAP), and Claim: (c) rapamycin or a rapamycin derivative capable of forming a ternary complex with the first and second proteins. Claim: 2. The crystalline composition of claim 1, wherein the first protein comprises the peptide sequence of SEQ ID No. 1 and the second protein comprises the peptide sequence of SEQ ID No. 2. Claim: 3. The composition of any of claims 1 or 2 in which the proteins of the complex are characterized by the coordinates of FIG. 4, or by coordinates having a root mean square deviation therefrom, with respect to conserved backbone atoms of the listed amino acids, of not more than 1.5 .ANG.. Current U.S. Class: 530/350; 536/231; 536/235 Current International Class: C07K 1447 Other References: Choi et al. "Structure of the FKBP12-Rapamycin complex interacting with the binding domain of human FRAP" Science 273, 239-242, Jul. 12, 1996. ; Van Duyne "Atomic structure of the human immunophilin FKBP-12 complex with FK506 and rapamycin" J. Mol. Biol. 229, 105-124, 1993. ; Wilson et al. Comparative X-ray structure of the major binding protein for the immunosuppressant FK506 . . . Acta Cryst. D51, 551-521, 1995. Primary Examiner: Wax, Robert A. Assistant Examiner: Nashed, Nashaat T. Attorney, Agent or Firm: Berstein, David L.

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Crystalline FRAP complex