PDBsum entry 2i2c

Transferase

PDB id: 2i2c

Contents

Protein chain

264 a.a. *

Ligands

DTA

PG4

Waters ×133

* Residue conservation analysis

PDB id:

2i2c

Name:

Transferase

Title:

Crystal structure of lmnadk1

Structure:

Probable inorganic polyphosphate/atp-NAD kinase 1. Chain: a. Synonym: polyp, /atp NAD kinase 1. Engineered: yes

Source:

Listeria monocytogenes egd-e. Organism_taxid: 169963. Strain: egd-e. Gene: ppnk1. Expressed in: escherichia coli. Expression_system_taxid: 562.

Resolution:

1.85Å R-factor: 0.192 R-free: 0.210

Authors:

G.Poncet-Montange,G.Labesse

Key ref:

G.Poncet-Montange et al. (2007). NAD kinases use substrate-assisted catalysis for specific recognition of NAD. J Biol Chem, 282, 33925-33934. PubMed id: 17686780 DOI: 10.1074/jbc.M701394200

Date:

16-Aug-06 Release date: 07-Aug-07

Protein chain

Q8Y8D7  (NADK1_LISMO) -  NAD kinase 1 from Listeria monocytogenes serovar 1/2a (strain ATCC BAA-679 / EGD-e)

Seq: 264 a.a.

Struc: 264 a.a.

Enzyme reactions

• Enzyme class: E.C.2.7.1.23 - NAD(+) kinase.
• Reaction: NAD⁺ + ATP = ADP + NADP⁺ + H⁺

Molecule diagrams generated from .mol files obtained from the KEGG ftp site

reference

DOI no: 10.1074/jbc.M701394200

J Biol Chem 282:33925-33934 (2007)

PubMed id: 17686780

NAD kinases use substrate-assisted catalysis for specific recognition of NAD.

G.Poncet-Montange, L.Assairi, S.Arold, S.Pochet, G.Labesse.

ABSTRACT

Here we describe the crystal structures of the NAD kinase (LmNADK1) from Listeria monocytogenes in complex with its substrate NAD, its product NADP, or two synthesized NAD mimics. We identified one of the NAD mimics, di-adenosine diphosphate, as a new substrate for LmNADK1, whereas we showed that the closely related compound di-5'-thioadenosine is a novel non-natural inhibitor for this enzyme. These structures suggest a mechanism involving substrate-assisted catalysis. Indeed, sequence/structure comparison and directed mutagenesis have previously shown that NAD kinases (NADKs) and the distantly related 6-phosphofructokinases share the same catalytically important GGDGT motif. However, in this study we have shown that these enzymes use the central aspartate of this motif differently. Although this acidic residue chelates the catalytic Mg(2+) ion in 6-phosphofructokinases, it activates the phospho-acceptor (NAD) in NADKs. Sequence/structure comparisons suggest that the role of this aspartate would be conserved in NADKs and the related sphingosine and diacylglycerol kinases.

Selected figure(s)

Figure 1.
Schematic reaction and chemical structures of nucleotides described in this study.A, schematic reaction of the NADKs. B, dinucleotides linked by a diphosphate group and representation of adenine and nicotinamide moiety. C, dinucleotide linked by a disulfide bridge (DTA) and its protected form (TAA).

Figure 3.
Stereo view of the superposed N-terminal domains of NADKs and PFKs. The N termini of LmNADK1 and E. coli PFK were superposed using the program ViTO (33). The picture was generated by the program PYMOL. Gray and black schematics and wireframes represent E. coli PFK/ADP/FBP/Mg^2+ and LmNADK1/NAD, respectively.

The above figures are reprinted by permission from the ASBMB: J Biol Chem (2007, 282, 33925-33934) copyright 2007.

Figures were selected by an automated process.