Crystalline FRAP complex

• US 5,939,528 A
• Filed: 10/31/1997
• Issued: 08/17/1999
• Est. Priority Date: 10/23/1996
• Status: Expired due to Term

• Current Assignee: Cornell Research Foundation Incorporated (Cornell University)
• Original Assignee: Cornell Research Foundation Incorporated (Cornell University)
• Inventors: Clardy, Jon C., Choi, Jungwon
• Primary Examiner(s): Wax, Robert A.
• Assistant Examiner(s): Nashed, Nashaat T.
• Application Number:
  US08/963,601
• Time in Patent Office: 655 Days
• Field of Search: 530/350, 536/23.1, 536/23.5
• US Class Current: 530/350
• CPC Class Codes: C07K 14/47 from mammals
• CPC Class Codes: C12N 9/1205 Phosphotransferases with an alcohol group as acceptor (2.7.1), e.g. protein kinases

Abstract

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.

Claims

1. An orthorhombic crystalline composition in the space group P2₁ 2₁ 2₁ which diffracts X-rays at a resolution of 2.7 Å

or better, each asymmetric unit of which containing one complex comprising;

(a) a first protein comprising a peptide sequence derived or selected from the peptide sequence of human FK506 binding protein 12 (FKBP12),

(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

(c) rapamycin or a rapamycin derivative capable of forming a ternary complex with the first and second proteins.

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.

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 Å

.