PDBsum entry 5ml0

Transcription

PDB id

5ml0

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Contents

			Protein chain

					108 a.a.

			Ligands

					P2L


					EDO ×2

			Waters ×220

PDB id:

5ml0

Links

Name:

Transcription

Title:

Bromodomain of mouse pcaf with (r)-4-chloro-2-methyl-5-((1- methylpiperidin-3-yl)amino)pyridazin-3(2h)-one

Structure:

Histone acetyltransferase kat2b. Chain: a. Synonym: histone acetyltransferase pcaf,histone acetylase pcaf,lysine acetyltransferase 2b,p300/cbp-associated factor,p/caf. Engineered: yes

Source:

Mus musculus. Mouse. Organism_taxid: 10090. Gene: kat2b, pcaf. Expressed in: escherichia coli. Expression_system_taxid: 562

Resolution:

1.64Å

R-factor:

0.181

R-free:

0.222

Authors:

C.-W.Chung

Key ref:

P.G.Humphreys et al. (2017). Discovery of a Potent, Cell Penetrant, and Selective p300/CBP-Associated Factor (PCAF)/General Control Nonderepressible 5 (GCN5) Bromodomain Chemical Probe. J Med Chem, 60, 695-709. PubMed id: 28002667 DOI: 10.1021/acs.jmedchem.6b01566

Date:

05-Dec-16

Release date:

20-Dec-17

PROCHECK

	Headers

	References

Protein chain

Q9JHD1 (KAT2B_MOUSE) - Histone acetyltransferase KAT2B from Mus musculus

Seq: Struc:

Seq: Struc:					813 a.a. 108 a.a.

Key:

PfamA domain

Secondary structure



		Enzyme reactions

Enzyme class 1:

E.C.2.3.1.48 - histone acetyltransferase.

[IntEnz] [ExPASy] [KEGG] [BRENDA]

Reaction:

L-lysyl-[protein] + acetyl-CoA = N₆-acetyl-L-lysyl-[protein] + CoA + H⁺

L-lysyl-[protein]	+	acetyl-CoA	=	N(6)-acetyl-L-lysyl-[protein]	+	CoA	+	H(+)

Enzyme class 2:

E.C.2.3.1.57 - diamine N-acetyltransferase.

[IntEnz] [ExPASy] [KEGG] [BRENDA]

Reaction:

an alkane-alpha,omega-diamine + acetyl-CoA = an N-acetylalkane- alpha,omega-diamine + CoA + H⁺

alkane-alpha,omega-diamine	+	acetyl-CoA	=	N-acetylalkane- alpha,omega-diamine	+	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

reference

DOI no: 10.1021/acs.jmedchem.6b01566	J Med Chem 60:695-709 (2017)
PubMed id: 28002667

Discovery of a Potent, Cell Penetrant, and Selective p300/CBP-Associated Factor (PCAF)/General Control Nonderepressible 5 (GCN5) Bromodomain Chemical Probe.
P.G.Humphreys, P.Bamborough, C.W.Chung, P.D.Craggs, L.Gordon, P.Grandi, T.G.Hayhow, J.Hussain, K.L.Jones, M.Lindon, A.M.Michon, J.F.Renaux, C.J.Suckling, D.F.Tough, R.K.Prinjha.

ABSTRACT

p300/CREB binding protein associated factor (PCAF/KAT2B) and general control nonderepressible 5 (GCN5/KAT2A) are multidomain proteins that have been implicated in retroviral infection, inflammation pathways, and cancer development. However, outside of viral replication, little is known about the dependence of these effects on the C-terminal bromodomain. Herein, we report GSK4027 as a chemical probe for the PCAF/GCN5 bromodomain, together with GSK4028 as an enantiomeric negative control. The probe was optimized from a weakly potent, nonselective pyridazinone hit to deliver high potency for the PCAF/GCN5 bromodomain, high solubility, cellular target engagement, and ≥18000-fold selectivity over the BET family, together with ≥70-fold selectivity over the wider bromodomain families.