PDBsum entry 6cw3

Gene regulation

PDB id: 6cw3

Contents

Protein chains

222 a.a.

213 a.a.

199 a.a.

120 a.a.

191 a.a.

92 a.a.

Metals

_ZN ×4

Waters ×662

PDB id:

6cw3

Name:

Gene regulation

Title:

Crystal structure of a yeast saga transcriptional coactivator ada2/gcn5 hat subcomplex, crystal form 2

Structure:

Antibody heavy chain. Chain: a, c. Engineered: yes. Antibody light chain. Chain: b, d. Engineered: yes. Histone acetyltransferase gcn5. Chain: f, h. Engineered: yes.

Source:

Homo sapiens. Human. Organism_taxid: 9606. Expressed in: escherichia coli. Expression_system_taxid: 562. Saccharomyces cerevisiae s288c. Baker's yeast. Organism_taxid: 559292. Strain: atcc 204508 / s288c.

Resolution:

1.98Å R-factor: 0.204 R-free: 0.227

Authors:

J.Sun,M.Paduch,S.A.Kim,R.M.Kramer,A.F.Barrios,V.Lu,J.Luke,S.Usatyuk, A.A.Kossiakoff,S.Tan

Key ref:

J.Sun et al. (2018). Structural basis for activation of SAGA histone acetyltransferase Gcn5 by partner subunit Ada2. Proc Natl Acad Sci U S A, 115, 10010-10015. PubMed id: 30224453 DOI: 10.1073/pnas.1805343115

Date:

29-Mar-18 Release date: 19-Sep-18

Protein chains

No UniProt id for this chain

Struc: 222 a.a.

Protein chains

No UniProt id for this chain

Struc: 213 a.a.

Protein chain

Q03330  (GCN5_YEAST) -  Histone acetyltransferase GCN5 from Saccharomyces cerevisiae (strain ATCC 204508 / S288c)

Seq: 439 a.a.

Struc: 199 a.a.

Protein chain

Q02336  (ADA2_YEAST) -  Transcriptional adapter 2 from Saccharomyces cerevisiae (strain ATCC 204508 / S288c)

Seq: 434 a.a.

Struc: 120 a.a.*

Protein chain

Q03330  (GCN5_YEAST) -  Histone acetyltransferase GCN5 from Saccharomyces cerevisiae (strain ATCC 204508 / S288c)

Seq: 439 a.a.

Struc: 191 a.a.

Protein chain

Q02336  (ADA2_YEAST) -  Transcriptional adapter 2 from Saccharomyces cerevisiae (strain ATCC 204508 / S288c)

Seq: 434 a.a.

Struc: 92 a.a.

* PDB and UniProt seqs differ at 1 residue position (black cross)

Enzyme reactions

• Enzyme class 1: Chains F, H: E.C.2.3.1.- - ?????
• Enzyme class 2: Chains F, H: 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: 10.1073/pnas.1805343115

Proc Natl Acad Sci U S A 115:10010-10015 (2018)

PubMed id: 30224453

Structural basis for activation of SAGA histone acetyltransferase Gcn5 by partner subunit Ada2.

J.Sun, M.Paduch, S.A.Kim, R.M.Kramer, A.F.Barrios, V.Lu, J.Luke, S.Usatyuk, A.A.Kossiakoff, S.Tan.

ABSTRACT

The Gcn5 histone acetyltransferase (HAT) subunit of the SAGA transcriptional coactivator complex catalyzes acetylation of histone H3 and H2B N-terminal tails, posttranslational modifications associated with gene activation. Binding of the SAGA subunit partner Ada2 to Gcn5 activates Gcn5's intrinsically weak HAT activity on histone proteins, but the mechanism for this activation by the Ada2 SANT domain has remained elusive. We have employed Fab antibody fragments as crystallization chaperones to determine crystal structures of a yeast Ada2/Gcn5 complex. Our structural and biochemical results indicate that the Ada2 SANT domain does not activate Gcn5's activity by directly affecting histone peptide binding as previously proposed. Instead, the Ada2 SANT domain enhances Gcn5 binding of the enzymatic cosubstrate acetyl-CoA. This finding suggests a mechanism for regulating chromatin modification enzyme activity: controlling binding of the modification cosubstrate instead of the histone substrate.