PDBsum entry 1wug

Transferase

PDB id: 1wug

Contents

Protein chain

118 a.a. *

Ligands

NP1

* Residue conservation analysis

PDB id:

1wug

Name:

Transferase

Title:

Complex structure of pcaf bromodomain with small chemical ligand np1

Structure:

Histone acetyltransferase pcaf. Chain: a. Fragment: bromodomain. Synonym: p300/cbp-associated factor, p/caf, histone acetylase pcaf. Engineered: yes

Source:

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

NMR struc:

1 models

Authors:

L.Zeng,J.Li,M.Muller,S.Yan,S.Mujtaba,C.Pan,Z.Wang,M.M.Zhou

Key ref:

L.Zeng et al. (2005). Selective small molecules blocking HIV-1 Tat and coactivator PCAF association. J Am Chem Soc, 127, 2376-2377. PubMed id: 15724976 DOI: 10.1021/ja044885g

Date:

07-Dec-04 Release date: 16-Aug-05

Protein chain

Q92831  (KAT2B_HUMAN) -  Histone acetyltransferase KAT2B from Homo sapiens

Seq: 832 a.a.

Struc: 118 a.a.*

* PDB and UniProt seqs differ at 3 residue positions (black crosses)

Enzyme reactions

• Enzyme class 1: E.C.2.3.1.48 - histone acetyltransferase.
• Reaction: L-lysyl-[protein] + acetyl-CoA = N₆-acetyl-L-lysyl-[protein] + CoA + H⁺
• Enzyme class 2: E.C.2.3.1.57 - diamine N-acetyltransferase.
• Reaction: an alkane-alpha,omega-diamine + acetyl-CoA = an 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/ja044885g

J Am Chem Soc 127:2376-2377 (2005)

PubMed id: 15724976

Selective small molecules blocking HIV-1 Tat and coactivator PCAF association.

L.Zeng, J.Li, M.Muller, S.Yan, S.Mujtaba, C.Pan, Z.Wang, M.M.Zhou.

ABSTRACT

Development of drug resistance from mutations in the targeted viral proteins leads to continuation of viral production by chronically infected cells, contributing to HIV-mediated immune dysfunction. Targeting a host cell protein essential for viral reproduction, rather than a viral protein, may minimize the viral drug resistance problem as observed with HIV protease inhibitors. We report here the development of a novel class of N1-aryl-propane-1,3-diamine compounds using a structure-based approach that selectively inhibit the activity of the bromodomain of the human transcriptional co-activator PCAF, of which association with the HIV trans-activator Tat is essential for transcription and replication of the integrated HIV provirus.