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PDBsum entry 2ql6
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Signaling protein,transferase
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PDB id
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2ql6
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References listed in PDB file
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Key reference
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Title
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Crystal structure of human nicotinamide riboside kinase.
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Authors
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J.A.Khan,
S.Xiang,
L.Tong.
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Ref.
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Structure, 2007,
15,
1005-1013.
[DOI no: ]
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PubMed id
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Abstract
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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.
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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).
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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).
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The above figures are
reprinted
by permission from Cell Press:
Structure
(2007,
15,
1005-1013)
copyright 2007.
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