5H86

Human Gcn5 bound to butyryl-CoA

Summary for 5H86

• Entry DOI: 10.2210/pdb5h86/pdb
• Descriptor: Histone acetyltransferase KAT2A, Butyryl Coenzyme A, 1,2-ETHANEDIOL, ... (4 entities in total)
• Functional Keywords: gcn5, coenzyme a, transferase
• Biological source: Homo sapiens (Human)
• Total number of polymer chains: 1
• Total formula weight: 20306.35

Authors

Wolberger, C.,Ringel, A.E. (deposition date: 2015-12-23, release date: 2016-03-23, Last modification date: 2023-09-27)

Primary citation

Ringel, A.E.,Wolberger, C.
Structural basis for acyl-group discrimination by human Gcn5L2.
Acta Crystallogr D Struct Biol, 72:841-848, 2016

PubMed Abstract: Gcn5 is a conserved acetyltransferase that regulates transcription by acetylating the N-terminal tails of histones. Motivated by recent studies identifying a chemically diverse array of lysine acyl modifications in vivo, the acyl-chain specificity of the acetyltransferase human Gcn5 (Gcn5L2) was examined. Whereas Gcn5L2 robustly catalyzes lysine acetylation, the acyltransferase activity of Gcn5L2 becomes progressively weaker with increasing acyl-chain length. To understand how Gcn5 discriminates between different acyl-CoA molecules, structures of the catalytic domain of human Gcn5L2 bound to propionyl-CoA and butyryl-CoA were determined. Although the active site of Gcn5L2 can accommodate propionyl-CoA and butyryl-CoA without major structural rearrangements, butyryl-CoA adopts a conformation incompatible with catalysis that obstructs the path of the incoming lysine residue and acts as a competitive inhibitor of Gcn5L2 versus acetyl-CoA. These structures demonstrate how Gcn5L2 discriminates between acyl-chain donors and explain why Gcn5L2 has weak activity for acyl moieties that are larger than an acetyl group.

PubMed: 27377381
DOI: 10.1107/S2059798316007907

Experimental method

X-RAY DIFFRACTION (2.08 Å)