4LX9

Archaeal amino-terminal acetyltransferase (NAT) bound to acetyl coenzyme A

Summary for 4LX9

• Entry DOI: 10.2210/pdb4lx9/pdb
• Related: 2X7B 3TFY 4KVM 4KVO 4KVX
• Descriptor: ARCHAEAL AMINO-TERMINAL ACETYLTRANSFERASE, ACETYL COENZYME *A, ZINC ION, ... (4 entities in total)
• Functional Keywords: transferase, amino-terminal acetyltransferase, gnat fold, amino-terminal acetyltransferase (nat)
• Biological source: Sulfolobus solfataricus
• Cellular location: Cytoplasm (Potential): Q980R9
• Total number of polymer chains: 1
• Total formula weight: 20413.95

Authors

Liszczak, G.P.,Marmorstein, R. (deposition date: 2013-07-29, release date: 2013-08-21, Last modification date: 2024-02-28)

Primary citation

Liszczak, G.,Marmorstein, R.
Implications for the evolution of eukaryotic amino-terminal acetyltransferase (NAT) enzymes from the structure of an archaeal ortholog.
Proc.Natl.Acad.Sci.USA, 110:14652-14657, 2013

PubMed Abstract: Amino-terminal acetylation is a ubiquitous modification in eukaryotes that is involved in a growing number of biological processes. There are six known eukaryotic amino-terminal acetyltransferases (NATs), which are differentiated from one another on the basis of substrate specificity. To date, two eukaryotic NATs, NatA and NatE, have been structurally characterized, of which NatA will acetylate the α-amino group of a number of nonmethionine amino-terminal residue substrates such as serine; NatE requires a substrate amino-terminal methionine residue for activity. Interestingly, these two NATs use different catalytic strategies to accomplish substrate-specific acetylation. In archaea, where this modification is less prevalent, only one NAT enzyme has been identified. Surprisingly, this enzyme is able to acetylate NatA and NatE substrates and is believed to represent an ancestral NAT variant from which the eukaryotic NAT machinery evolved. To gain insight into the evolution of NAT enzymes, we determined the X-ray crystal structure of an archaeal NAT from Sulfolobus solfataricus (ssNAT). Through the use of mutagenesis and kinetic analysis, we show that the active site of ssNAT represents a hybrid of the NatA and NatE active sites, and we highlight features of this protein that allow it to facilitate catalysis of distinct substrates through different catalytic strategies, which is a unique characteristic of this enzyme. Taken together, the structural and biochemical data presented here have implications for the evolution of eukaryotic NAT enzymes and the substrate specificities therein.

PubMed: 23959863
DOI: 10.1073/pnas.1310365110

Experimental method

X-RAY DIFFRACTION (1.98 Å)