PDBsum entry 2ql6

Signaling protein,transferase

PDB id: 2ql6

Contents

Protein chain

(+ 10 more) 179 a.a. *

Ligands

ADP ×16

TIZ ×16

* Residue conservation analysis

PDB id:

2ql6

Name:

Signaling protein,transferase

Title:

Human nicotinamide riboside kinase (nrk1)

Structure:

Nicotinamide riboside kinase 1. Chain: a, b, c, d, e, f, g, h, i, j, k, l, m, n, o, p. Synonym: nrk1. Engineered: yes

Source:

Homo sapiens. Human. Organism_taxid: 9606. Gene: nrk1, c9orf95. Expressed in: escherichia coli. Expression_system_taxid: 562.

Resolution:

2.70Å R-factor: 0.207 R-free: 0.235

Authors:

J.A.Khan,S.Xiang,L.Tong

Key ref:

J.A.Khan et al. (2007). Crystal structure of human nicotinamide riboside kinase. Structure, 15, 1005-1013. PubMed id: 17698003 DOI: 10.1016/j.str.2007.06.017

Date:

12-Jul-07 Release date: 02-Oct-07

Protein chains

Q9NWW6  (NRK1_HUMAN) -  Nicotinamide riboside kinase 1 from Homo sapiens

Seq: 199 a.a.

Struc: 179 a.a.

Enzyme reactions

• Enzyme class 2: E.C.2.7.1.173 - nicotinate riboside kinase.
• Reaction: beta-D-ribosylnicotinate + ATP = nicotinate beta-D-ribonucleotide + ADP + H⁺

beta-D-ribosylnicotinate + ATP = nicotinate beta-D-ribonucleotide (Bound ligand (Het Group name = ADP) corresponds exactly) + ADP + H(+)

• Enzyme class 3: E.C.2.7.1.22 - ribosylnicotinamide kinase.
• Reaction: beta-nicotinamide D-riboside + ATP = beta-nicotinamide D-ribonucleotide + ADP + H⁺

beta-nicotinamide D-riboside + ATP = beta-nicotinamide D-ribonucleotide (Bound ligand (Het Group name = ADP) corresponds exactly) + ADP + 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

reference

DOI no: 10.1016/j.str.2007.06.017

Structure 15:1005-1013 (2007)

PubMed id: 17698003

Crystal structure of human nicotinamide riboside kinase.

J.A.Khan, S.Xiang, L.Tong.

ABSTRACT

Nicotinamide riboside kinase (NRK) has an important role in the biosynthesis of NAD(+) as well as the activation of tiazofurin and other NR analogs for anticancer therapy. NRK belongs to the deoxynucleoside kinase and nucleoside monophosphate (NMP) kinase superfamily, although the degree of sequence conservation is very low. We report here the crystal structures of human NRK1 in a binary complex with the reaction product nicotinamide mononucleotide (NMN) at 1.5 A resolution and in a ternary complex with ADP and tiazofurin at 2.7 A resolution. The active site is located in a groove between the central parallel beta sheet core and the LID and NMP-binding domains. The hydroxyl groups on the ribose of NR are recognized by Asp56 and Arg129, and Asp36 is the general base of the enzyme. Mutation of residues in the active site can abolish the catalytic activity of the enzyme, confirming the structural observations.

Selected figure(s)

Figure 4.
Figure 4. The Binding Modes of NMN and Tiazofurin
(A) The binding site for NMN. Hydrogen-bonding interactions are indicated with blue, dashed lines. The binding mode of tiazofurin is also shown (in black).
(B) Molecular surface of the active-site region of NRK1, colored based on electrostatic potential.
(C) Final 2F[o] − F[c] electron density for tiazofurin at 2.7 Å resolution. Contoured at 1σ.
(A) and (C) were produced with PyMOL (DeLano, 2002); (B) was produced with Grasp (Nicholls et al., 1991).

Figure 5.
Figure 5. The Binding Mode of ADP
(A) Final 2F[o] − F[c] electron density for ADP at 2.7 Å resolution. Contoured at 1σ.
(B) The binding site for ADP. Hydrogen-bonding interactions are indicated with blue, dashed lines.
(C) Overlay of the structures of the binary complex with NMN (in gray) and the ternary complex with ADP:tiazofurin.
This figure was produced with PyMOL (DeLano, 2002).

The above figures are reprinted by permission from Cell Press: Structure (2007, 15, 1005-1013) copyright 2007.

Figures were selected by an automated process.