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Transferase PDB id
1nut
Jmol
Contents
Protein chains
212 a.a. *
Ligands
SO4 ×2
APC ×2
Waters ×251
* Residue conservation analysis
PDB id:
1nut
Name: Transferase
Title: Crystal structure of human cytosolic nmn/namn adenylyltransf complexed with atp analog
Structure: Fksg76. Chain: a, b. Synonym: nmn/namn adenylyltransferase. Engineered: yes
Source: Homo sapiens. Human. Organism_taxid: 9606. Gene: fksg76. Expressed in: escherichia coli. Expression_system_taxid: 562.
Biol. unit: Tetramer (from PDB file)
Resolution:
1.90Å     R-factor:   0.198     R-free:   0.236
Authors: X.Zhang,O.V.Kurnasov,S.Karthikeyan,N.V.Grishin,A.L.Osterman,
Key ref:
X.Zhang et al. (2003). Structural characterization of a human cytosolic NMN/NaMN adenylyltransferase and implication in human NAD biosynthesis. J Biol Chem, 278, 13503-13511. PubMed id: 12574164 DOI: 10.1074/jbc.M300073200
Date:
01-Feb-03     Release date:   03-Jun-03    
PROCHECK
Go to PROCHECK summary
 Headers
 References

Protein chains
Pfam   ArchSchema ?
Q96T66  (NMNA3_HUMAN) -  Nicotinamide mononucleotide adenylyltransferase 3
Seq:
Struc: 		252 a.a.
212 a.a.*
Key:    PfamA domain  Secondary structure  CATH domain
* PDB and UniProt seqs differ at 1 residue position (black cross)

 Enzyme reactions 
   Enzyme class 2: E.C.2.7.7.1  - Nicotinamide-nucleotide adenylyltransferase.
[IntEnz]   [ExPASy]   [KEGG]   [BRENDA]
      Reaction: ATP + nicotinamide ribonucleotide = diphosphate + NAD+
ATP
Bound ligand (Het Group name = APC)
matches with 55.00% similarity 		+ nicotinamide ribonucleotide
 = diphosphate
 + NAD(+)
   Enzyme class 3: E.C.2.7.7.18  - Nicotinate-nucleotide adenylyltransferase.
[IntEnz]   [ExPASy]   [KEGG]   [BRENDA]
      Reaction: ATP + nicotinate ribonucleotide = diphosphate + deamido-NAD+
ATP
Bound ligand (Het Group name = APC)
matches with 55.00% similarity 		+ nicotinate ribonucleotide
 = diphosphate
 + deamido-NAD(+)
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
 Gene Ontology (GO) functional annotation 
  GO annot!
  Cellular component     mitochondrion   2 terms 
  Biological process     biosynthetic process   6 terms 
  Biochemical function     nucleotide binding     6 terms  

 

 
    reference    
 
 
DOI no: 10.1074/jbc.M300073200 J Biol Chem 278:13503-13511 (2003)
PubMed id: 12574164  
 
 
Structural characterization of a human cytosolic NMN/NaMN adenylyltransferase and implication in human NAD biosynthesis.
X.Zhang, O.V.Kurnasov, S.Karthikeyan, N.V.Grishin, A.L.Osterman, H.Zhang.
 
  ABSTRACT  
 
Pyridine dinucleotides (NAD and NADP) are ubiquitous cofactors involved in hundreds of redox reactions essential for the energy transduction and metabolism in all living cells. In addition, NAD also serves as a substrate for ADP-ribosylation of a number of nuclear proteins, for silent information regulator 2 (Sir2)-like histone deacetylase that is involved in gene silencing regulation, and for cyclic ADP ribose (cADPR)-dependent Ca(2+) signaling. Pyridine nucleotide adenylyltransferase (PNAT) is an indispensable central enzyme in the NAD biosynthesis pathways catalyzing the condensation of pyridine mononucleotide (NMN or NaMN) with the AMP moiety of ATP to form NAD (or NaAD). Here we report the identification and structural characterization of a novel human PNAT (hsPNAT-3) that is located in the cytoplasm and mitochondria. Its subcellular localization and tissue distribution are distinct from the previously identified human nuclear PNAT-1 and PNAT-2. Detailed structural analysis of PNAT-3 in its apo form and in complex with its substrate(s) or product revealed the catalytic mechanism of the enzyme. The characterization of the cytosolic human PNAT-3 provided compelling evidence that the final steps of NAD biosynthesis pathways may exist in mammalian cytoplasm and mitochondria, potentially contributing to their NAD/NADP pool.
 
  Selected figure(s)  
 
Figure 3.
Fig. 3. The overall structure of hsPNAT-3. A, stereo view of the C[ ]trace of hsPNAT-3 monomer (red) superimposed with hsPNAT-1 (blue). Every 20th residue is labeled. B, stereo diagrams of hsPNAT-3 tetramer. Each monomer is colored differently. The disordered regions are shown as dotted loops. Two orthogonal views are shown. The bound NAD molecules are shown as ball-and-stick representations. 		Figure 5.
Fig. 5. The ATP and NMN binding sites in hsPNAT-3. A, stereo view of the ATP binding site. B, the F[o] F[c] omit map for NMN molecule in monomer B of the NMN binary complex showing the alternative conformations of NMN phosphate. The map is contoured at 2 . C, stereo view of the NMN binding site. The substrates ATP and NMN and a bound sulfate molecule are shown as bonds colored according to atom types. The two alternative conformations of the bound NMN are shown. Relevant protein residues are shown in ball-and-stick representation. The hydrogen bonds are indicated by dotted lines.
 
  The above figures are reprinted by permission from the ASBMB: J Biol Chem (2003, 278, 13503-13511) copyright 2003.  
  Figures were selected by an automated process.  

Literature references that cite this PDB file's key reference

  PubMed id Reference
20857400 J.Bi, H.Wang, and J.Xie (2011).
Comparative genomics of NAD(P) biosynthesis and novel antibiotic drug targets.
  J Cell Physiol, 226, 331-340.  
20126265 J.Gilley, and M.P.Coleman (2010).
Endogenous Nmnat2 is an essential survival factor for maintenance of healthy axons.
  PLoS Biol, 8, e1000300.  
20954240 L.Brunetti, M.Di Stefano, S.Ruggieri, F.Cimadamore, and G.Magni (2010).
Homology modeling and deletion mutants of human nicotinamide mononucleotide adenylyltransferase isozyme 2: new insights on structure and function relationship.
  Protein Sci, 19, 2440-2450.  
20857515 Y.Feng, T.Yan, J.Zheng, X.Ge, Y.Mu, Y.Zhang, D.Wu, J.L.Du, and Q.Zhai (2010).
Overexpression of Wld(S) or Nmnat2 in mauthner cells by single-cell electroporation delays axon degeneration in live zebrafish.
  J Neurosci Res, 88, 3319-3327.  
  19372760 J.Wang, and Z.He (2009).
NAD and axon degeneration: from the Wlds gene to neurochemistry.
  Cell Adh Migr, 3, 77-87.  
19716475 L.Sorci, Y.Pan, Y.Eyobo, I.Rodionova, N.Huang, O.Kurnasov, S.Zhong, A.D.MacKerell, H.Zhang, and A.L.Osterman (2009).
Targeting NAD biosynthesis in bacterial pathogens: Structure-based development of inhibitors of nicotinate mononucleotide adenylyltransferase NadD.
  Chem Biol, 16, 849-861.
PDB code: 3hfj
19448972 R.G.Zhai, M.Rizzi, and S.Garavaglia (2009).
Nicotinamide/nicotinic acid mononucleotide adenylyltransferase, new insights into an ancient enzyme.
  Cell Mol Life Sci, 66, 2805-2818.  
19410549 T.Nakagawa, D.J.Lomb, M.C.Haigis, and L.Guarente (2009).
SIRT5 Deacetylates carbamoyl phosphate synthetase 1 and regulates the urea cycle.
  Cell, 137, 560-570.  
18977360 V.C.Sershon, B.D.Santarsiero, and A.D.Mesecar (2009).
Kinetic and X-ray structural evidence for negative cooperativity in substrate binding to nicotinate mononucleotide adenylyltransferase (NMAT) from Bacillus anthracis.
  J Mol Biol, 385, 867-888.
PDB codes: 2qtm 2qtn 2qtr
18823127 E.S.Burgos, and V.L.Schramm (2008).
Weak coupling of ATP hydrolysis to the chemical equilibrium of human nicotinamide phosphoribosyltransferase.
  Biochemistry, 47, 11086-11096.  
18275811 N.Huang, L.Sorci, X.Zhang, C.A.Brautigam, X.Li, N.Raffaelli, G.Magni, N.V.Grishin, A.L.Osterman, and H.Zhang (2008).
Bifunctional NMN adenylyltransferase/ADP-ribose pyrophosphatase: structure and function in bacterial NAD metabolism.
  Structure, 16, 196-209.
PDB codes: 2qjo 2qjt 2r5w
18344983 R.G.Zhai, F.Zhang, P.R.Hiesinger, Y.Cao, C.M.Haueter, and H.J.Bellen (2008).
NAD synthase NMNAT acts as a chaperone to protect against neurodegeneration.
  Nature, 452, 887-891.  
17564960 F.Liu, A.Arias-Vásquez, K.Sleegers, Y.S.Aulchenko, M.Kayser, P.Sanchez-Juan, B.J.Feng, A.M.Bertoli-Avella, J.van Swieten, T.I.Axenovich, P.Heutink, C.van Broeckhoven, B.A.Oostra, and C.M.van Duijn (2007).
A genomewide screen for late-onset Alzheimer disease in a genetically isolated Dutch population.
  Am J Hum Genet, 81, 17-31.  
17335512 G.Wang, and E.Pichersky (2007).
Nicotinamidase participates in the salvage pathway of NAD biosynthesis in Arabidopsis.
  Plant J, 49, 1020-1029.  
17207927 H.Jia, T.Yan, Y.Feng, C.Zeng, X.Shi, and Q.Zhai (2007).
Identification of a critical site in Wld(s): essential for Nmnat enzyme activity and axon-protective function.
  Neurosci Lett, 413, 46-51.  
17270012 S.N.Hashida, H.Takahashi, M.Kawai-Yamada, and H.Uchimiya (2007).
Arabidopsis thaliana nicotinate/nicotinamide mononucleotide adenyltransferase (AtNMNAT) is required for pollen tube growth.
  Plant J, 49, 694-703.  
16959969 P.O.Hassa, S.S.Haenni, M.Elser, and M.O.Hottiger (2006).
Nuclear ADP-ribosylation reactions in mammalian cells: where are we today and where are we going?
  Microbiol Mol Biol Rev, 70, 789-829.  
17132048 R.G.Zhai, Y.Cao, P.R.Hiesinger, Y.Zhou, S.Q.Mehta, K.L.Schulze, P.Verstreken, and H.J.Bellen (2006).
Drosophila NMNAT maintains neural integrity independent of its NAD synthesis activity.
  PLoS Biol, 4, e416.  
16585762 S.Y.Gerdes, O.V.Kurnasov, K.Shatalin, B.Polanuyer, R.Sloutsky, V.Vonstein, R.Overbeek, and A.L.Osterman (2006).
Comparative genomics of NAD biosynthesis in cyanobacteria.
  J Bacteriol, 188, 3012-3023.  
15807656 M.Ziegler (2005).
The adenine nucleotide translocase--a carrier protein potentially required for mitochondrial generation of NAD.
  Biochemistry (Mosc), 70, 173-177.  
12815723 A.Rongvaux, F.Andris, F.Van Gool, and O.Leo (2003).
Reconstructing eukaryotic NAD metabolism.
  Bioessays, 25, 683-690.  
The most recent references are shown first. Citation data come partly from CiteXplore and partly from an automated harvesting procedure. Note that this is likely to be only a partial list as not all journals are covered by either method. However, we are continually building up the citation data so more and more references will be included with time. Where a reference describes a PDB structure, the PDB code is shown on the right.