PDBsum entry 5r8h

Signaling protein

PDB id: 5r8h

Contents

Protein chain

152 a.a.

Ligands

SO4 ×2

T91

Waters ×113

PDB id:

5r8h

Name:

Signaling protein

Title:

Pandda analysis group deposition interleukin-1 beta -- fragment z111716368 in complex with interleukin-1 beta

Structure:

Interleukin-1 beta. Chain: a. Synonym: il-1 beta,catabolin. Engineered: yes

Source:

Homo sapiens. Human. Organism_taxid: 9606. Gene: il1b, il1f2. Expressed in: escherichia coli. Expression_system_taxid: 562

Resolution:

1.50Å R-factor: 0.192 R-free: 0.223

Authors:

G.F.De Nicola,C.E.Nichols

Key ref:

C.Nichols et al. (2020). Mining the PDB for Tractable Cases Where X-ray Crystallography Combined with Fragment Screens Can Be Used to Systematically Design Protein-Protein Inhibitors: Two Test Cases Illustrated by IL1β-IL1R and p38α-TAB1 Complexes. J Med Chem, 63, 7559-7568. PubMed id: 32543856 DOI: 10.1021/acs.jmedchem.0c00403

Date:

03-Mar-20 Release date: 22-Apr-20

Protein chain

P01584  (IL1B_HUMAN) -  Interleukin-1 beta from Homo sapiens

Seq: 269 a.a.

Struc: 152 a.a.

DOI no: 10.1021/acs.jmedchem.0c00403

J Med Chem 63:7559-7568 (2020)

PubMed id: 32543856

Mining the PDB for Tractable Cases Where X-ray Crystallography Combined with Fragment Screens Can Be Used to Systematically Design Protein-Protein Inhibitors: Two Test Cases Illustrated by IL1β-IL1R and p38α-TAB1 Complexes.

C.Nichols, J.Ng, A.Keshu, G.Kelly, M.R.Conte, M.S.Marber, F.Fraternali, G.F.De Nicola.

ABSTRACT

Nowadays, it is possible to combine X-ray crystallography and fragment screening in a medium throughput fashion to chemically probe the surfaces used by proteins to interact and use the outcome of the screens to systematically design protein-protein inhibitors. To prove it, we first performed a bioinformatics analysis of the Protein Data Bank protein complexes, which revealed over 400 cases where the crystal lattice of the target in the free form is such that large portions of the interacting surfaces are free from lattice contacts and therefore accessible to fragments during soaks. Among the tractable complexes identified, we then performed single fragment crystal screens on two particular interesting cases: the Il1β-ILR and p38α-TAB1 complexes. The result of the screens showed that fragments tend to bind in clusters, highlighting the small-molecule hotspots on the surface of the target protein. In most of the cases, the hotspots overlapped with the binding sites of the interacting proteins.