PDBsum entry 6gps

Signaling protein

PDB id: 6gps

Contents

Protein chain

330 a.a.

Ligands

F7N

Metals

_ZN

PDB id:

6gps

Name:

Signaling protein

Title:

Crystal structure of ccr2a in complex with mk-0812

Structure:

C-c chemokine receptor type 2,rubredoxin,c-c chemokine receptor type 2. Chain: a. Fragment: rubredoxin inserted into ccr2a between residue 231 and 235, rubredoxin inserted into ccr2a between residue 231 and 235,rubredoxin inserted into ccr2a between residue 231 and 235,rubredoxin inserted into ccr2a between residue 231 and 235,rubredoxin inserted into ccr2a between residue 231 and 235,rubredoxin inserted into ccr2a between residue 231 and 235,rubredoxin inserted into ccr2a between residue

Source:

Homo sapiens, clostridium pasteurianum. Human. Organism_taxid: 9606, 1501. Gene: ccr2, cmkbr2. Expressed in: spodoptera frugiperda. Expression_system_taxid: 7108

Resolution:

3.30Å R-factor: 0.245 R-free: 0.296

Authors:

A.Pautsch,G.Schnapp

Key ref:

A.K.Apel et al. (2019). Crystal Structure of CC Chemokine Receptor 2A in Complex with an Orthosteric Antagonist Provides Insights for the Design of Selective Antagonists. Structure, 27, 427. PubMed id: 30581043 DOI: 10.1016/j.str.2018.10.027

Date:

07-Jun-18 Release date: 02-Jan-19

Protein chain

P00268  (RUBR_CLOPA) -  Rubredoxin from Clostridium pasteurianum

Seq: 54 a.a.

Struc: 330 a.a.

Protein chain

P41597  (CCR2_HUMAN) -  C-C chemokine receptor type 2 from Homo sapiens

Seq: 374 a.a.

Struc: 330 a.a.*

* PDB and UniProt seqs differ at 57 residue positions (black crosses)

DOI no: 10.1016/j.str.2018.10.027

Structure 27:427 (2019)

PubMed id: 30581043

Crystal Structure of CC Chemokine Receptor 2A in Complex with an Orthosteric Antagonist Provides Insights for the Design of Selective Antagonists.

A.K.Apel, R.K.Y.Cheng, C.S.Tautermann, M.Brauchle, C.Y.Huang, A.Pautsch, M.Hennig, H.Nar, G.Schnapp.

ABSTRACT

We determined two crystal structures of the chemokine receptor CCR2A in complex with the orthosteric antagonist MK-0812. Full-length CCR2A, stabilized by rubredoxin and a series of five mutations were resolved at 3.3 Å. An N- and C-terminally truncated CCR2A construct was crystallized in an alternate crystal form, which yielded a 2.7 Å resolution structure using serial synchrotron crystallography. Our structures provide a clear structural explanation for the observed key role of residue E291^7.39 in high-affinity binding of several orthosteric CCR2 antagonists. By combining all the structural information collected, we generated models of co-structures for the structurally diverse pyrimidine amide class of CCR2 antagonists. Even though the representative Ex15 overlays well with MK-0812, it also interacts with the non-conserved H121^3.33, resulting in a significant selectivity over CCR5. Insights derived from this work will facilitate drug discovery efforts directed toward highly selective CCR2 antagonists with potentially superior efficacy.