PDBsum entry 2x2c

Isomerase/immunosuppressant

PDB id: 2x2c

Contents

Protein chains

11 a.a.

165 a.a. *

Waters ×497

* Residue conservation analysis

PDB id:

2x2c

Name:

Isomerase/immunosuppressant

Title:

Acetyl-cypa:cyclosporine complex

Structure:

Cyclosporin a. Chain: b, f, l, p, r. Synonym: ciclosporin, ciclosporine. Engineered: yes. Peptidyl-prolyl cis-trans isomerase a. Chain: k, m, o, q, s. Synonym: ppiase a, rotamase a, cyclophilin a, cyclosporin a-binding protein, cypa. Engineered: yes

Source:

Synthetic: yes. Tolypocladium inflatum. Organism_taxid: 29910. Homo sapiens. Human. Organism_taxid: 9606. Expressed in: escherichia coli. Expression_system_taxid: 562

Resolution:

2.41Å R-factor: 0.209 R-free: 0.264

Authors:

M.Lammers,H.Neumann,J.W.Chin,L.C.James

Key ref:

M.Lammers et al. (2010). Acetylation regulates cyclophilin A catalysis, immunosuppression and HIV isomerization. Nat Chem Biol, 6, 331-337. PubMed id: 20364129

Date:

12-Jan-10 Release date: 23-Mar-10

Protein chains

No UniProt id for this chain

Struc: 11 a.a.

Protein chains

P62937  (PPIA_HUMAN) -  Peptidyl-prolyl cis-trans isomerase A from Homo sapiens

Seq: 165 a.a.

Struc: 165 a.a.*

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

Enzyme reactions

• Enzyme class: Chains K, M, O, Q, S: 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

Nat Chem Biol 6:331-337 (2010)

PubMed id: 20364129

Acetylation regulates cyclophilin A catalysis, immunosuppression and HIV isomerization.

M.Lammers, H.Neumann, J.W.Chin, L.C.James.

ABSTRACT

Cyclophilin A (CypA) is a ubiquitous cis-trans prolyl isomerase with key roles in immunity and viral infection. CypA suppresses T-cell activation through cyclosporine complexation and is required for effective HIV-1 replication in host cells. We show that CypA is acetylated in diverse human cell lines and use a synthetically evolved acetyllysyl-tRNA synthetase/tRNA(CUA) pair to produce recombinant acetylated CypA in Escherichia coli. We determined atomic-resolution structures of acetylated CypA and its complexes with cyclosporine and HIV-1 capsid. Acetylation markedly inhibited CypA catalysis of cis to trans isomerization and stabilized cis rather than trans forms of the HIV-1 capsid. Furthermore, CypA acetylation antagonized the immunosuppressive effects of cyclosporine by inhibiting the sequential steps of cyclosporine binding and calcineurin inhibition. Our results reveal that acetylation regulates key functions of CypA in immunity and viral infection and provide a general set of mechanisms by which acetylation modulates interactions to regulate cell function.