2ql6

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==Overview==
==Overview==
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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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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.
==About this Structure==
==About this Structure==
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[[Category: Homo sapiens]]
[[Category: Homo sapiens]]
[[Category: Single protein]]
[[Category: Single protein]]
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[[Category: Khan, J.A.]]
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[[Category: Khan, J A.]]
[[Category: Tong, L.]]
[[Category: Tong, L.]]
[[Category: Xiang, S.]]
[[Category: Xiang, S.]]
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[[Category: transferase]]
[[Category: transferase]]
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Wed Jan 23 13:21:33 2008''
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 18:40:08 2008''

Revision as of 16:40, 21 February 2008


2ql6, resolution 2.700Å

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human nicotinamide riboside kinase (NRK1)

Overview

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.

About this Structure

2QL6 is a Single protein structure of sequence from Homo sapiens with and as ligands. Full crystallographic information is available from OCA.

Reference

Crystal structure of human nicotinamide riboside kinase., Khan JA, Xiang S, Tong L, Structure. 2007 Aug;15(8):1005-13. PMID:17698003

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