PDBsum entry 6o1v

Hydrolase

PDB id: 6o1v

Contents

Protein chains

1179 a.a.

17 a.a.

Ligands

LJP

ATP ×2

POV ×5

CLR

Metals

_MG ×2

PDB id:

6o1v

Name:

Hydrolase

Title:

Complex of human cystic fibrosis transmembrane conductance regulator (cftr) and glpg1837

Structure:

Cystic fibrosis transmembrane conductance regulator. Chain: a. Synonym: cftr,atp-binding cassette sub-family c member 7,channel conductance-controlling atpase,camp-dependent chloride channel. Engineered: yes. Unknown peptide. Chain: b. Engineered: yes

Source:

Homo sapiens. Human. Organism_taxid: 9606. Gene: cftr, abcc7. Expressed in: homo sapiens. Expression_system_taxid: 9606. Expression_system_taxid: 9606

Authors:

Z.Zhang,F.Liu,J.Chen,A.Levit,B.Shoichet

Key ref:

F.Liu et al. (2019). Structural identification of a hotspot on CFTR for potentiation. Science, 364, 1184-1188. PubMed id: 31221859 DOI: 10.1126/science.aaw7611

Date:

21-Feb-19 Release date: 26-Jun-19

Protein chain

P13569  (CFTR_HUMAN) -  Cystic fibrosis transmembrane conductance regulator from Homo sapiens

Seq: 1480 a.a.

Struc: 1179 a.a.*

Protein chain

No UniProt id for this chain

Struc: 17 a.a.

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

Enzyme reactions

• Enzyme class: Chain A: E.C.5.6.1.6 - channel-conductance-controlling ATPase.
• Reaction: ATP + H2O + closed Cl^- channel = ADP + phosphate + open Cl^- channel

ATP (Bound ligand (Het Group name = ATP) corresponds exactly) + H2O + closed Cl(-) channel = ADP + phosphate + open Cl(-) channel

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

reference

DOI no: 10.1126/science.aaw7611

Science 364:1184-1188 (2019)

PubMed id: 31221859

Structural identification of a hotspot on CFTR for potentiation.

F.Liu, Z.Zhang, A.Levit, J.Levring, K.K.Touhara, B.K.Shoichet, J.Chen.

ABSTRACT

Cystic fibrosis is a fatal disease caused by mutations in the cystic fibrosis transmembrane conductance regulator (CFTR). Two main categories of drugs are being developed: correctors that improve folding of CFTR and potentiators that recover the function of CFTR. Here, we report two cryo-electron microscopy structures of human CFTR in complex with potentiators: one with the U.S. Food and Drug Administration (FDA)-approved drug ivacaftor at 3.3-angstrom resolution and the other with an investigational drug, GLPG1837, at 3.2-angstrom resolution. These two drugs, although chemically dissimilar, bind to the same site within the transmembrane region. Mutagenesis suggests that in both cases, hydrogen bonds provided by the protein are important for drug recognition. The molecular details of how ivacaftor and GLPG1837 interact with CFTR may facilitate structure-based optimization of therapeutic compounds.