1OG3

Crystal structure of the eukaryotic mono-ADP-ribosyltransferase ART2.2 mutant E189I in complex with NAD

Summary for 1OG3

• Entry DOI: 10.2210/pdb1og3/pdb
• Related: 1GXY 1GXZ 1GY0 1OG1 1OG4
• Descriptor: T-CELL ECTO-ADP-RIBOSYLTRANSFERASE 2, NICOTINAMIDE-ADENINE-DINUCLEOTIDE (3 entities in total)
• Functional Keywords: transferase, adp-ribosyltransferase, immuno-regulation
• Biological source: RATTUS NORVEGICUS (RAT)
• Cellular location: Cell membrane; Lipid-anchor, GPI-anchor: P20974
• Total number of polymer chains: 1
• Total formula weight: 26715.92

Authors

Ritter, H.,Koch-Nolte, F.,Marquez, V.E.,Schulz, G.E. (deposition date: 2003-04-24, release date: 2003-08-28, Last modification date: 2024-10-23)

Primary citation

Ritter, H.,Koch-Nolte, F.,Marquez, V.E.,Schulz, G.E.
Substrate Binding and Catalysis of Ecto-Adp-Ribosyltransferase 2.2 From Rat
Biochemistry, 42:10155-, 2003

PubMed Abstract: The structures of beta-methylenethiazole-4-carboxamide adenine dinucleotide (TAD), NAD(+), and NADH as bound to ecto-ADP-ribosyltransferase 2.2 from rat and to its mutants E189I and E189A, respectively, have been established. The positions and conformations of NAD(+) and its analogues agree in general with those in other ADP-ribosyltransferases. The kinetic constants for NAD(+) hydrolysis were determined by RP-HPLC. The specific activity amounts to 26 units/mg, which is 6000-fold higher than a previously reported rate and 500-fold higher than the hydrolysis rates of other ADP-ribosyltransferases, confirming that hydrolysis is the major function of this enzyme. On the basis of structures and mutant activities, a catalytic mechanism is proposed. The known auto-ADP-ribosylation of the enzyme at the suggested position R184 is supported by one of the crystal structures where the nucleophile position is occupied by an Neta atom of this arginine which in turn is backed up by the base E159.

PubMed: 12939142
DOI: 10.1021/BI034625W

Experimental method

X-RAY DIFFRACTION (2.6 Å)