PDBsum entry 4fap

Cell cycle

PDB id: 4fap

Contents

Protein chains

107 a.a. *

94 a.a. *

Ligands

ARD

* Residue conservation analysis

PDB id:

4fap

Name:

Cell cycle

Title:

Atomic structures of the rapamycin analogs in complex with both human fkbp12 and frb domain of frap

Structure:

Fk506-binding protein. Chain: a. Synonym: fkbp12. Engineered: yes. Fkbp12-rapamycin associated protein. Chain: b. Fragment: frb. Synonym: frap

Source:

Homo sapiens. Human. Organism_taxid: 9606. Strain: bl21 (de3) (novagen). Gene: human hippocampal cdna library source 8 (clontech, palo alto, ca). Expressed in: escherichia coli. Expression_system_taxid: 562. Organism_taxid: 9606

Resolution:

2.80Å R-factor: 0.184 R-free: 0.266

Authors:

J.Liang,J.Clardy

Key ref:

J.Liang et al. (1999). Refined structure of the FKBP12-rapamycin-FRB ternary complex at 2.2 A resolution. Acta Crystallogr D Biol Crystallogr, 55, 736-744. PubMed id: 10089303 DOI: 10.1107/S0907444998014747

Date:

06-May-99 Release date: 13-Sep-00

Protein chain

P62942  (FKB1A_HUMAN) -  Peptidyl-prolyl cis-trans isomerase FKBP1A from Homo sapiens

Seq: 108 a.a.

Struc: 107 a.a.

Protein chain

P42345  (MTOR_HUMAN) -  Serine/threonine-protein kinase mTOR from Homo sapiens

Seq: 2549 a.a.

Struc: 94 a.a.

Enzyme reactions

• Enzyme class 2: Chain A: E.C.5.2.1.8 - peptidylprolyl isomerase.
• Reaction: [protein]-peptidylproline (omega=180) = [protein]-peptidylproline (omega=0)
• Enzyme class 3: Chain B: E.C.2.7.11.1 - non-specific serine/threonine protein kinase.
• Reaction:
  1. L-seryl-[protein] + ATP = O-phospho-L-seryl-[protein] + ADP + H⁺
  2. L-threonyl-[protein] + ATP = O-phospho-L-threonyl-[protein] + ADP + H⁺

Note, where more than one E.C. class is given (as above), each may correspond to a different protein domain or, in the case of polyprotein precursors, to a different mature protein.

Molecule diagrams generated from .mol files obtained from the KEGG ftp site

reference

DOI no: 10.1107/S0907444998014747

Acta Crystallogr D Biol Crystallogr 55:736-744 (1999)

PubMed id: 10089303

Refined structure of the FKBP12-rapamycin-FRB ternary complex at 2.2 A resolution.

J.Liang, J.Choi, J.Clardy.

ABSTRACT

The structure of the FKBP12-rapamycin-FRB ternary complex has now been refined at 2.2 A resolution. The cell-cycle arrest agent rapamycin binds FK506-binding protein (FKBP12) and the FKBP12-rapamycin binding (FRB) domain of FKBP12-rapamycin associated protein (FRAP) simultaneously, and the inhibition of FRAP is responsible for rapamycin's biological activity. The conformation of rapamycin in the ternary complex is very similar to that observed in the FKBP12-rapamycin binary complex, with an r.m.s. difference of only 0.30 A. However, a slight (9 degrees ) rotation repositions the FRB-binding face of rapamycin in the ternary complex. There are extensive rapamycin-protein interactions and relatively few interactions between the two protein partners FKBP12 and FRB, these interactions mainly involving residues in the 40s and 80s loops of FKBP12 and alpha1 and alpha4 of FRB. The high-resolution refinement has revealed the crucial role of several buried waters in the formation of the ternary complex.

Selected figure(s)

Figure 1.
Figure 1 Chemical structures of (a) FK506 and (b) rapamycin, showing the regions interacting with FKBP12 and FRB or calcineurin (effector region).

Figure 2.
Figure 2 Stereoviews of (a) the rapamycin-binding pocket of FRB and (b) the rapamycin-binding pocket of FKBP12. Hydrogen bonds between rapamycin and FKBP12 are indicated by dashed lines, the ligand is in bold lines and the protein has light lines and residue labels.

The above figures are reprinted by permission from the IUCr: Acta Crystallogr D Biol Crystallogr (1999, 55, 736-744) copyright 1999.

Figures were selected by an automated process.