PDBsum entry 2ppo

Lyase

PDB id: 2ppo

Contents

Protein chain

107 a.a. *

Waters ×137

* Residue conservation analysis

PDB id:

2ppo

Name:

Lyase

Title:

Crystal structure of e60a mutant of fkbp12

Structure:

Fk506-binding protein 1a. Chain: a. Synonym: peptidyl-prolyl cis-trans isomerase, ppiase, rotamase, 12 kda fkbp, fkbp-12, immunophilin fkbp12. Engineered: yes. Mutation: yes

Source:

Homo sapiens. Human. Organism_taxid: 9606. Gene: fkbp1a, fkbp1, fkbp12. Expressed in: escherichia coli. Expression_system_taxid: 562

Resolution:

1.29Å R-factor: 0.189 R-free: 0.182

Authors:

S.Szep,S.Park,G.D.Vanduyne,J.G.Saven

Key ref:

S.Szep et al. (2008). Structural coupling between FKBP12 and buried water. Proteins, 74, 603-611. PubMed id: 18704951 DOI: 10.1002/prot.22176

Date:

30-Apr-07 Release date: 27-May-08

Protein chain

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

Seq: 108 a.a.

Struc: 107 a.a.*

* PDB and UniProt seqs differ at 1 residue position (black cross)

Enzyme reactions

• Enzyme class: E.C.5.2.1.8 - peptidylprolyl isomerase.
• Reaction: [protein]-peptidylproline (omega=180) = [protein]-peptidylproline (omega=0)

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

Added reference

DOI no: 10.1002/prot.22176

Proteins 74:603-611 (2008)

PubMed id: 18704951

Structural coupling between FKBP12 and buried water.

S.Szep, S.Park, E.T.Boder, G.D.Van Duyne, J.G.Saven.

ABSTRACT

Globular proteins often contain structurally well-resolved internal water molecules. Previously, we reported results from a molecular dynamics study that suggested that buried water (Wat3) may play a role in modulating the structure of the FK506 binding protein-12 (FKBP12) (Park and Saven, Proteins 2005; 60:450-463). In particular, simulations suggested that disrupting a hydrogen bond to Wat3 by mutating E60 to either A or Q would cause a structural perturbation involving the distant W59 side chain, which rotates to a new conformation in response to the mutation. This effectively remodels the ligand-binding pocket, as the side chain in the new conformation is likely to clash with bound FK506. To test whether the protein structure is in effect modulated by the binding of a buried water in the distance, we determined high-resolution (0.92-1.29 A) structures of wild-type FKBP12 and its two mutants (E60A, E60Q) by X-ray crystallography. The structures of mutant FKBP12 show that the ligand-binding pocket is indeed remodeled as predicted by the substitution at position 60, even though the water molecule does not directly interact with any of the amino acids of the binding pocket. Thus, these structures support the view that buried water molecules constitute an integral, noncovalent component of the protein structure. Additionally, this study provides an example in which predictions from molecular dynamics simulations are experimentally validated with atomic precision, thus showing that the structural features of protein-water interactions can be reliably modeled at a molecular level. Proteins 2009. (c) 2008 Wiley-Liss, Inc.

Selected figure(s)

Figure 3.
Figure 3. The N-terminus of the helix moves toward the center of the protein, with the main chain atoms from W59 and A60 of the mutant moving by 1.28-1.74 Å (dotted lines). (Inset) The C[ ]trace of the E60A mutant (cyan) is shown against the surface rendering of wild-type FKBP12 (purple), which is partially cut away to reveal the protein core.

Figure 5.
Figure 5. (a) FK506 (from PDB 1FKF) modeled in the ligand-binding pocket of wild-type (violet) and E60Q (cyan) FKBP12. The rotation of W59 leads to a conformation that creates steric clash between its side chain and the docked FK506. (b) The network of interacting amino acids and Wat3 in FKBP12.

The above figures are reprinted by permission from John Wiley & Sons, Inc.: Proteins (2008, 74, 603-611) copyright 2008.

Figures were selected by an automated process.