PDBsum entry 5lpm

Transcription

PDB id: 5lpm

Contents

Protein chains

116 a.a.

Ligands

71Y ×4

ACT ×3

Waters ×333

PDB id:

5lpm

Name:

Transcription

Title:

Crystal structure of the bromodomain of human ep300 bound to the inhibitor xdm3d

Structure:

Histone acetyltransferase p300. Chain: a, b. Fragment: bromodomain, unp residues 1048-1161. Synonym: p300 hat,e1a-associated protein p300. Engineered: yes

Source:

Homo sapiens. Human. Organism_taxid: 9606. Gene: ep300, p300. Expressed in: escherichia coli bl21(de3). Expression_system_taxid: 469008.

Resolution:

1.50Å R-factor: 0.159 R-free: 0.187

Authors:

M.Huegle,D.Wohlwend,S.Gerhardt

Key ref:

M.Hügle et al. (2017). Beyond the BET Family: Targeting CBP/p300 with 4-Acyl Pyrroles. Angew Chem Int Ed Engl, 56, 12476-12480. PubMed id: 28766825 DOI: 10.1002/anie.201705516

Date:

13-Aug-16 Release date: 16-Aug-17

Protein chains

Q09472  (EP300_HUMAN) -  Histone acetyltransferase p300 from Homo sapiens

Seq: 2414 a.a.

Struc: 116 a.a.*

* PDB and UniProt seqs differ at 2 residue positions (black crosses)

Enzyme reactions

• Enzyme class 1: E.C.2.3.1.- - ?????
• Enzyme class 2: E.C.2.3.1.48 - histone acetyltransferase.
• Reaction: L-lysyl-[protein] + acetyl-CoA = N₆-acetyl-L-lysyl-[protein] + CoA + H⁺

Note, where more than one E.C. class is given (as above), each may correspond to a different protein domain or, in the case of polyprotein precursors, to a different mature protein.

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

Added reference

DOI no: 10.1002/anie.201705516

Angew Chem Int Ed Engl 56:12476-12480 (2017)

PubMed id: 28766825

Beyond the BET Family: Targeting CBP/p300 with 4-Acyl Pyrroles.

M.Hügle, X.Lucas, D.Ostrovskyi, P.Regenass, S.Gerhardt, O.Einsle, M.Hau, M.Jung, B.Breit, S.Günther, D.Wohlwend.

ABSTRACT

Bromodomain and extra-terminal domain (BET) inhibitors are widely used both as chemical tools to study the biological role of their targets in living organisms and as candidates for drug development against several cancer variants and human disorders. However, non-BET bromodomains such as those in p300 and CBP are less studied. XDM-CBP is a highly potent and selective inhibitor for the bromodomains of CBP and p300 derived from a pan-selective BET BRD-binding fragment. Along with X-ray crystal-structure analysis and thermodynamic profiling, XDM-CBP was used in screenings of several cancer cell lines in vitro to study its inhibitory potential on cancer cell proliferation. XDM-CBP is demonstrated to be a potent and selective CBP/p300 inhibitor that acts on specific cancer cell lines, in particular malignant melanoma, breast cancer, and leukemia.