4MXE

Human ESCO1 (Eco1/Ctf7 ortholog), acetyltransferase domain in complex with acetyl-CoA

Summary for 4MXE

• Entry DOI: 10.2210/pdb4mxe/pdb
• Descriptor: N-acetyltransferase ESCO1, ACETYL COENZYME *A (3 entities in total)
• Functional Keywords: structural genomics, structural genomics consortium, sgc, gcn5-related n-acetyltransferase fold, acetyltransferase, nucleus, transferase
• Biological source: Homo sapiens (human)
• Cellular location: Nucleus : Q5FWF5
• Total number of polymer chains: 2
• Total formula weight: 49616.83

Authors

Karlberg, T.,Wisniewska, M.,Thorsell, A.G.,Kouznetsova, E.,Arrowsmith, C.H.,Berglund, H.,Bountra, C.,Collins, R.,Edwards, A.M.,Flodin, S.,Flores, A.,Graslund, S.,Hammarstrom, M.,Johansson, I.,Kallas, A.,Kraulis, P.,Kotenyova, T.,Moche, M.,Nielsen, T.K.,Nordlund, P.,Nyman, T.,Persson, C.,Schutz, P.,Svensson, L.,Tresaugues, L.,Van Den Berg, S.,Wahlberg, E.,Weigelt, J.,Welin, M.,Schuler, H.,Structural Genomics Consortium (SGC) (deposition date: 2013-09-26, release date: 2015-04-08, Last modification date: 2024-11-06)

Primary citation

Kouznetsova, E.,Kanno, T.,Karlberg, T.,Thorsell, A.G.,Wisniewska, M.,Kursula, P.,Sjogren, C.,Schuler, H.
Sister Chromatid Cohesion Establishment Factor ESCO1 Operates by Substrate-Assisted Catalysis.
Structure, 24:789-796, 2016

PubMed Abstract: Sister chromatid cohesion, formed by the cohesin protein complex, is essential for chromosome segregation. In order for cohesion to be established, the cohesin subunit SMC3 needs to be acetylated by a homolog of the ESCO1/Eco1 acetyltransferases, the enzymatic mechanism of which has remained unknown. Here we report the crystal structure of the ESCO1 acetyltransferase domain in complex with acetyl-coenzyme A, and show by SAXS that ESCO1 is a dimer in solution. The structure reveals an active site that lacks a potential catalytic base side chain. However, mutation of glutamate 789, a surface residue that is close to the automodification target lysine 803, strongly reduces autoacetylation of ESCO1. Moreover, budding yeast Smc3 mutated at the conserved residue D114, adjacent to the cohesion-activating acetylation site K112,K113, cannot be acetylated in vivo. This indicates that ESCO1 controls cohesion through substrate-assisted catalysis. Thus, this study discloses a key mechanism for cohesion establishment.

PubMed: 27112597
DOI: 10.1016/j.str.2016.03.021

Experimental method

X-RAY DIFFRACTION (2.6 Å)