PDBsum entry 1uux

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protein ligands metals links
Chelatase PDB id
Protein chain
161 a.a. *
Waters ×155
* Residue conservation analysis
PDB id:
Name: Chelatase
Title: Structure of a molybdopterin-bound cnx1g domain links molybdenum and copper metabolism
Structure: Molybdopterin biosynthesis cnx1. Chain: a. Fragment: g-domain, residues 462-624. Synonym: cnx1. Engineered: yes
Source: Arabidopsis thaliana. Mouse-ear cress. Organism_taxid: 3702. Expressed in: escherichia coli. Expression_system_taxid: 562.
Biol. unit: Trimer (from PDB file)
1.60Å     R-factor:   0.165     R-free:   0.191
Authors: J.Kuper,A.Llamas,H.J.Hecht,R.R.Mendel,G.Schwarz
Key ref:
J.Kuper et al. (2004). Structure of the molybdopterin-bound Cnx1G domain links molybdenum and copper metabolism. Nature, 430, 803-806. PubMed id: 15306815 DOI: 10.1038/nature02681
12-Jan-04     Release date:   09-Aug-04    
Go to PROCHECK summary

Protein chain
Pfam   ArchSchema ?
Q39054  (CNX1_ARATH) -  Molybdopterin biosynthesis protein CNX1
670 a.a.
161 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.  - Molybdopterin molybdotransferase.
[IntEnz]   [ExPASy]   [KEGG]   [BRENDA]
      Reaction: Adenylyl-molybdopterin + molybdate = molybdenum cofactor + AMP
+ molybdate
= molybdenum cofactor
      Cofactor: Zinc or magnesium
   Enzyme class 3: E.C.  - Molybdopterin adenylyltransferase.
[IntEnz]   [ExPASy]   [KEGG]   [BRENDA]
      Reaction: ATP + molybdopterin = diphosphate + adenylyl-molybdopterin
+ molybdopterin
= diphosphate
+ adenylyl-molybdopterin
      Cofactor: Manganese or magnesium
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!
  Biological process     Mo-molybdopterin cofactor biosynthetic process   1 term 


DOI no: 10.1038/nature02681 Nature 430:803-806 (2004)
PubMed id: 15306815  
Structure of the molybdopterin-bound Cnx1G domain links molybdenum and copper metabolism.
J.Kuper, A.Llamas, H.J.Hecht, R.R.Mendel, G.Schwarz.
The molybdenum cofactor is part of the active site of all molybdenum-dependent enzymes, except nitrogenase. The molybdenum cofactor consists of molybdopterin, a phosphorylated pyranopterin, with an ene-dithiolate coordinating molybdenum. The same pyranopterin-based cofactor is involved in metal coordination of the homologous tungsten-containing enzymes found in archea. The molybdenum cofactor is synthesized by a highly conserved biosynthetic pathway. In plants, the multidomain protein Cnx1 catalyses the insertion of molybdenum into molybdopterin. The Cnx1 G domain (Cnx1G), whose crystal structure has been determined in its apo form, binds molybdopterin with high affinity and participates in the catalysis of molybdenum insertion. Here we present two high-resolution crystal structures of Cnx1G in complex with molybdopterin and with adenylated molybdopterin (molybdopterin-AMP), a mechanistically important intermediate. Molybdopterin-AMP is the reaction product of Cnx1G and is subsequently processed in a magnesium-dependent reaction by the amino-terminal E domain of Cnx1 to yield active molybdenum cofactor. The unexpected identification of copper bound to the molybdopterin dithiolate sulphurs in both structures, coupled with the observed copper inhibition of Cnx1G activity, provides a molecular link between molybdenum and copper metabolism.
  Selected figure(s)  
Figure 1.
Figure 1: Structure of the Cnx1G -MPT and Ser583Ala -MPT -AMP complexes. a, b, Ribbon representation of Cnx1G (a) and Ser583Ala (b). -Helices and -strands are shown in green and orange, respectively. Bound MPT and MPT -AMP are shown in ball-and-stick notation and are covered by the 2F[o] -F[c] electron density contoured at 1.0 . The difference density (F[o] -F[c]) is shown in red (3.5 ). c, d, Close-up views of the bound MPT (c) and AMP (d) regions in the Ser583Ala structure. e, f, Molecular surface of Ser583Ala with bound MPT -AMP showing, respectively, residues important for MPT binding (red) and catalysis12,14 (blue), and the electrostatic surface potential with 11 kT as borders for electropositive (blue) and negative (red) regions calculated with SYBIL and GRASP30. The catalytically important residues Asp 515 and Asp 548 are highlighted. The position of Mg2+ found in the homologous MoeA^22 domain is superimposed.
Figure 4.
Figure 4: Hypothetical mechanism of the molybdenum insertion reaction. The mechanism of copper chelation is unknown. Cnx1G adenylates Cu -MPT, a reaction that is thought to be cation (M2+) dependent. Cnx1E subsequently cleaves the Cu -MPT -AMP complex to activate and to transfer the molybdenum atom to MPT. The function of copper is seen in the protection of the reactive MPT dithiolate.
  The above figures are reprinted by permission from Macmillan Publishers Ltd: Nature (2004, 430, 803-806) copyright 2004.  
  Figures were selected by the author.  

Literature references that cite this PDB file's key reference

  PubMed id Reference
21031595 J.Reiss, and R.Hahnewald (2011).
Molybdenum cofactor deficiency: Mutations in GPHN, MOCS1, and MOCS2.
  Hum Mutat, 32, 10-18.  
20164445 J.Teschner, N.Lachmann, J.Schulze, M.Geisler, K.Selbach, J.Santamaria-Araujo, J.Balk, R.R.Mendel, and F.Bittner (2010).
A novel role for Arabidopsis mitochondrial ABC transporter ATM3 in molybdenum cofactor biosynthesis.
  Plant Cell, 22, 468-480.  
19887375 Y.Zhang, and V.N.Gladyshev (2010).
General trends in trace element utilization revealed by comparative genomic analyses of Co, Cu, Mo, Ni, and Se.
  J Biol Chem, 285, 3393-3405.  
19675644 G.Schwarz, R.R.Mendel, and M.W.Ribbe (2009).
Molybdenum cofactors, enzymes and pathways.
  Nature, 460, 839-847.  
19320747 J.B.Glass, F.Wolfe-Simon, and A.D.Anbar (2009).
Coevolution of metal availability and nitrogen assimilation in cyanobacteria and algae.
  Geobiology, 7, 100-123.  
19079350 K.J.Waldron, and N.J.Robinson (2009).
How do bacterial cells ensure that metalloproteins get the correct metal?
  Nat Rev Microbiol, 7, 25-35.  
19524482 R.Hänsch, and R.R.Mendel (2009).
Physiological functions of mineral micronutrients (Cu, Zn, Mn, Fe, Ni, Mo, B, Cl).
  Curr Opin Plant Biol, 12, 259-266.  
  19623604 R.R.Mendel (2009).
Cell biology of molybdenum.
  Biofactors, 35, 429-434.  
18096847 J.R.Andreesen, and K.Makdessi (2008).
Tungsten, the surprisingly positively acting heavy metal element for prokaryotes.
  Ann N Y Acad Sci, 1125, 215-229.  
18931123 S.J.Hall, A.Hitchcock, C.S.Butler, and D.J.Kelly (2008).
A Multicopper oxidase (Cj1516) and a CopA homologue (Cj1161) are major components of the copper homeostasis system of Campylobacter jejuni.
  J Bacteriol, 190, 8075-8085.  
17416894 A.Llamas, M.Tejada-Jimenez, D.González-Ballester, J.J.Higuera, G.Schwarz, A.Galván, and E.Fernández (2007).
Chlamydomonas reinhardtii CNX1E reconstitutes molybdenum cofactor biosynthesis in Escherichia coli mutants.
  Eukaryot Cell, 6, 1063-1067.  
17459792 C.Feng, G.Tollin, and J.H.Enemark (2007).
Sulfite oxidizing enzymes.
  Biochim Biophys Acta, 1774, 527-539.  
17198377 J.D.Nichols, S.Xiang, H.Schindelin, and K.V.Rajagopalan (2007).
Mutational analysis of Escherichia coli MoeA: two functional activities map to the active site cleft.
  Biochemistry, 46, 78-86.
PDB codes: 2nqk 2nqm 2nqn 2nqq 2nqr 2nqs 2nqu 2nqv 2nro 2nrp 2nrs
17686778 M.Neumann, W.Stöcklein, and S.Leimkühler (2007).
Transfer of the molybdenum cofactor synthesized by Rhodobacter capsulatus MoeA to XdhC and MobA.
  J Biol Chem, 282, 28493-28500.  
17687573 M.S.Morrison, P.A.Cobine, and E.L.Hegg (2007).
Probing the role of copper in the biosynthesis of the molybdenum cofactor in Escherichia coli and Rhodobacter sphaeroides.
  J Biol Inorg Chem, 12, 1129-1139.  
17898892 R.R.Mendel, A.G.Smith, A.Marquet, and M.J.Warren (2007).
Metal and cofactor insertion.
  Nat Prod Rep, 24, 963-971.  
17263774 S.Puig, N.Andrés-Colás, A.García-Molina, and L.Peñarrubia (2007).
Copper and iron homeostasis in Arabidopsis: responses to metal deficiencies, interactions and biotechnological applications.
  Plant Cell Environ, 30, 271-290.  
16636046 A.Llamas, T.Otte, G.Multhaup, R.R.Mendel, and G.Schwarz (2006).
The Mechanism of nucleotide-assisted molybdenum insertion into molybdopterin. A novel route toward metal cofactor assembly.
  J Biol Chem, 281, 18343-18350.  
16286471 A.Vergnes, J.Pommier, R.Toci, F.Blasco, G.Giordano, and A.Magalon (2006).
NarJ chaperone binds on two distinct sites of the aponitrate reductase of Escherichia coli to coordinate molybdenum cofactor insertion and assembly.
  J Biol Chem, 281, 2170-2176.  
16669776 G.Schwarz, and R.R.Mendel (2006).
Molybdenum cofactor biosynthesis and molybdenum enzymes.
  Annu Rev Plant Biol, 57, 623-647.  
17001074 I.Paarmann, B.Schmitt, B.Meyer, M.Karas, and H.Betz (2006).
Mass spectrometric analysis of glycine receptor-associated gephyrin splice variants.
  J Biol Chem, 281, 34918-34925.  
17003121 M.L.Schlief, T.West, A.M.Craig, D.M.Holtzman, and J.D.Gitlin (2006).
Role of the Menkes copper-transporting ATPase in NMDA receptor-mediated neuronal toxicity.
  Proc Natl Acad Sci U S A, 103, 14919-14924.  
16616609 M.Pilon, S.E.Abdel-Ghany, C.M.Cohu, K.A.Gogolin, and H.Ye (2006).
Copper cofactor delivery in plant cells.
  Curr Opin Plant Biol, 9, 256-263.  
15693047 A.F.Peacock, H.D.Batey, C.Raendler, A.C.Whitwood, R.N.Perutz, and A.K.Duhme-Klair (2005).
A metal-based lumophore tailored to sense biologically relevant oxometalates.
  Angew Chem Int Ed Engl, 44, 1712-1714.  
15632135 J.D.Nichols, and K.V.Rajagopalan (2005).
In vitro molybdenum ligation to molybdopterin using purified components.
  J Biol Chem, 280, 7817-7822.  
15710899 X.Dai, K.Hayashi, H.Nozaki, Y.Cheng, and Y.Zhao (2005).
Genetic and chemical analyses of the action mechanisms of sirtinol in Arabidopsis.
  Proc Natl Acad Sci U S A, 102, 3129-3134.  
15306795 W.N.Hunter (2004).
Biological chemistry: the making of Moco.
  Nature, 430, 736-737.  
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 codes are shown on the right.