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PDBsum entry 2e5c
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Contents |
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* Residue conservation analysis
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PDB id:
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Transferase
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Title:
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Crystal structure of human nmprtase complexed with 5'-phosphoribosyl- 1'-pyrophosphate
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Structure:
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Nicotinamide phosphoribosyltransferase. Chain: a, b. Synonym: namprtase, nampt, pre-b cell-enhancing factor, pre-b-cell colony-enhancing factor 1, visfatin. Engineered: yes
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Source:
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Homo sapiens. Human. Organism_taxid: 9606. Expressed in: escherichia coli. Expression_system_taxid: 562.
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Resolution:
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2.20Å
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R-factor:
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0.177
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R-free:
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0.221
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Authors:
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R.Takahashi,S.Nakamura,Y.Kobayashi,T.Ohkubo
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Key ref:
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R.Takahashi
et al.
(2010).
Structure and reaction mechanism of human nicotinamide phosphoribosyltransferase.
J Biochem (tokyo),
147,
95-107.
PubMed id:
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Date:
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20-Dec-06
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Release date:
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25-Dec-07
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PROCHECK
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Headers
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References
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P43490
(NAMPT_HUMAN) -
Nicotinamide phosphoribosyltransferase from Homo sapiens
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Seq:
Struc:
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491 a.a.
466 a.a.
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Key: |
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PfamA domain |
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Secondary structure |
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CATH domain |
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Enzyme class:
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E.C.2.4.2.12
- nicotinamide phosphoribosyltransferase.
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Reaction:
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beta-nicotinamide D-ribonucleotide + diphosphate = 5-phospho-alpha-D- ribose 1-diphosphate + nicotinamide + H+
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beta-nicotinamide D-ribonucleotide
Bound ligand (Het Group name = )
matches with 41.94% similarity
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+
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diphosphate
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=
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5-phospho-alpha-D- ribose 1-diphosphate
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+
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nicotinamide
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+
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H(+)
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Molecule diagrams generated from .mol files obtained from the
KEGG ftp site
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J Biochem (tokyo)
147:95-107
(2010)
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PubMed id:
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Structure and reaction mechanism of human nicotinamide phosphoribosyltransferase.
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R.Takahashi,
S.Nakamura,
T.Nakazawa,
K.Minoura,
T.Yoshida,
Y.Nishi,
Y.Kobayashi,
T.Ohkubo.
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ABSTRACT
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Nicotinamide (NM) phosphoribosyltransferase (NMPRTase) catalyzes the reaction of
NM and 5'-phosphoribosyl-1'-pyrophosphate (PRPP) to form NM mononucleotide (NMN)
and pyrophosphate (PPi) in the pathway of NAD-biosynthesis. Monitoring the (1)H
and (31)P NMR spectra of the reaction mixture, we found that this reaction is
reversible as dictated by the equilibrium constant K = [NMN][PPi]/([NM][PRPP]) =
0.14, which agreed well with the ratio of second-order rate constants for
forward and backward reactions, K = 0.16. The crystal structures of this enzyme
in the free form and bound to NM and PRPP at the resolution of 2.0-2.2 A were
essentially identical to that of the complex with NMN, except for some
variations that could facilitate the substitution reaction by fixing the
nucleophile and the leaving group for the requisite inversion of configuration
at the C1' carbon of the ribose ring. In the active site near the C1' atom of
the bound PRPP or NMN, there was neither negatively charged group nor waterproof
environment necessary to support the feasibility of a ribo-oxocarbocation
intermediate inherent in the S(N)1 mechanism. The structures and catalytic
mechanism thus revealed are also discussed in connection with the multiple
biological functions of NMPRTase.
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