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PDBsum entry 3dhd

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protein ligands metals Protein-protein interface(s) links
Transferase PDB id
3dhd
Jmol
Contents
Protein chains
464 a.a. *
Ligands
NMN ×2
POP ×2
Metals
_MG ×4
Waters ×359
* Residue conservation analysis
PDB id:
3dhd
Name: Transferase
Title: Crystal structure of human nampt complexed with nicotinamide mononucleotide and pyrophosphate
Structure: Nicotinamide phosphoribosyltransferase. Chain: a, b. Synonym: namprtase, nampt, pre-b cell-enhancing factor, pre-b-cell colony-enhancing factor 1, visfatin. Engineered: yes
Source: Homo sapiens. Organism_taxid: 9606. Gene: nampt, pbef, pbef1. Expressed in: escherichia coli. Expression_system_taxid: 562.
Resolution:
2.00Å     R-factor:   0.182     R-free:   0.221
Authors: M.Ho,E.S.Burgos,S.C.Almo,V.L.Schramm
Key ref:
E.S.Burgos et al. (2009). A phosphoenzyme mimic, overlapping catalytic sites and reaction coordinate motion for human NAMPT. Proc Natl Acad Sci U S A, 106, 13748-13753. PubMed id: 19666527 DOI: 10.1073/pnas.0903898106
Date:
17-Jun-08     Release date:   18-Aug-09    
PROCHECK
Go to PROCHECK summary
 Headers
 References

Protein chains
Pfam   ArchSchema ?
P43490  (NAMPT_HUMAN) -  Nicotinamide phosphoribosyltransferase
Seq:
Struc:
491 a.a.
464 a.a.
Key:    PfamA domain  Secondary structure  CATH domain

 Enzyme reactions 
   Enzyme class: E.C.2.4.2.12  - Nicotinamide phosphoribosyltransferase.
[IntEnz]   [ExPASy]   [KEGG]   [BRENDA]
      Reaction: Nicotinamide D-ribonucleotide + diphosphate = nicotinamide + 5-phospho- alpha-D-ribose 1-diphosphate
Nicotinamide D-ribonucleotide
Bound ligand (Het Group name = NMN)
corresponds exactly
+
diphosphate
Bound ligand (Het Group name = POP)
corresponds exactly
= nicotinamide
+ 5-phospho- alpha-D-ribose 1-diphosphate
Molecule diagrams generated from .mol files obtained from the KEGG ftp site
 Gene Ontology (GO) functional annotation 
  GO annot!
  Cellular component     extracellular region   6 terms 
  Biological process     small molecule metabolic process   14 terms 
  Biochemical function     protein binding     6 terms  

 

 
    reference    
 
 
DOI no: 10.1073/pnas.0903898106 Proc Natl Acad Sci U S A 106:13748-13753 (2009)
PubMed id: 19666527  
 
 
A phosphoenzyme mimic, overlapping catalytic sites and reaction coordinate motion for human NAMPT.
E.S.Burgos, M.C.Ho, S.C.Almo, V.L.Schramm.
 
  ABSTRACT  
 
Nicotinamide phosphoribosyltransferase (NAMPT) is highly evolved to capture nicotinamide (NAM) and replenish the nicotinamide adenine dinucleotide (NAD(+)) pool during ADP-ribosylation and transferase reactions. ATP-phosphorylation of an active-site histidine causes catalytic activation, increasing NAM affinity by 160,000. Crystal structures of NAMPT with catalytic site ligands identify the phosphorylation site, establish its role in catalysis, demonstrate unique overlapping ATP and phosphoribosyltransferase sites, and establish reaction coordinate motion. NAMPT structures with beryllium fluoride indicate a covalent H247-BeF(3)(-) as the phosphohistidine mimic. Activation of NAMPT by H247-phosphorylation causes stabilization of the enzyme-phosphoribosylpyrophosphate complex, permitting efficient capture of NAM. Reactant and product structures establish reaction coordinate motion for NAMPT to be migration of the ribosyl anomeric carbon from the pyrophosphate leaving group to the nicotinamide-N1 while the 5-phosphoryl group, the pyrophosphate moiety, and the nicotinamide ring remain fixed in the catalytic site.
 
  Selected figure(s)  
 
Figure 2.
The AMPcP-binding site of human NAMPT. (A) Ribbon diagram showing the AMPcP binding mode with H247-unmodified human NAMPT. The 2 monomers are colored in yellow and cyan, respectively. AMPcP is shown in black and water molecules are depicted as red spheres with hydrogen bonds represented as olive dashed lines. The 5.3 Å green dashed line represents the distance from (Nδ1)H247 to the methylene α,β-bridge of AMPcP. (B) The structural overlap for PRPP·BzAM (substrates shown as green sticks with an overall representation of the structure in light green) and AMPcP complexes in nonphosphorylated human NAMPT (black stick representation of AMPcP with the corresponding structure in gray) is demonstrated. Produced with PyMol v 1.1.
Figure 5.
Interaction between (Nδ1)H247-BeF[3]^− and the neighboring residues (cross-eye stereo representation). The structure of one monomer is in yellow, the other is in cyan, PRPP·BzAM is in black, Be is in lemon, and F is in light blue. Blue dashed lines represent Mg^2+ interactions with PRPP and BeF[3]^−, olive dashed lines represent interatomic distances L[1], L[2], and L[3] and green dashed lines represent distances d[1], d[2], d[3], and d[4] as summarized in Table 1. Produced with PyMol v 1.1.
 
  Figures were selected by an automated process.  

Literature references that cite this PDB file's key reference

  PubMed id Reference
19819904 R.Takahashi, S.Nakamura, T.Nakazawa, K.Minoura, T.Yoshida, Y.Nishi, Y.Kobayashi, and T.Ohkubo (2010).
Structure and reaction mechanism of human nicotinamide phosphoribosyltransferase.
  J Biochem, 147, 95.
PDB codes: 2e5b 2e5c 2e5d
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