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Oxidoreductase (pqq(a)-choh(d)) PDB id
4aah
Jmol
Contents
Protein chains
571 a.a. *
69 a.a. *
Ligands
PQQ ×2
Metals
_CA ×2
Waters ×521
* Residue conservation analysis
PDB id:
4aah
Name: Oxidoreductase (pqq(a)-choh(d))
Title: Methanol dehydrogenase from methylophilus w3a1
Structure: Methanol dehydrogenase. Chain: a, c. Synonym: medh. Methanol dehydrogenase. Chain: b, d. Synonym: medh. Ec: 1.1.99.8
Source: Methylophilus methylotrophus. Organism_taxid: 2327. Strain: w3a1. Strain: w3a1
Biol. unit: Tetramer (from PQS)
Resolution:
2.40Å     R-factor:   0.152    
Authors: F.S.Mathews,Z.-X.Xia
Key ref:
Z.Xia et al. (1996). Determination of the gene sequence and the three-dimensional structure at 2.4 angstroms resolution of methanol dehydrogenase from Methylophilus W3A1. J Mol Biol, 259, 480-501. PubMed id: 8676383 DOI: 10.1006/jmbi.1996.0334
Date:
10-Mar-96     Release date:   07-Dec-96    
Supersedes: 3aah
PROCHECK
Go to PROCHECK summary
 Headers
 References

Protein chains
Pfam   ArchSchema ?
P38539  (DHM1_METME) -  Methanol dehydrogenase [cytochrome c] subunit 1
Seq:
Struc: 		 
Seq:
Struc: 		573 a.a.
571 a.a.
Protein chains
Pfam   ArchSchema ?
P38540  (DHM2_METME) -  Methanol dehydrogenase [cytochrome c] subunit 2
Seq:
Struc: 		91 a.a.
69 a.a.
Key:    PfamA domain  Secondary structure  CATH domain

 Enzyme reactions 
   Enzyme class: Chains A, B, C, D: E.C.1.1.2.7  - Methanol dehydrogenase (cytochrome c).
[IntEnz]   [ExPASy]   [KEGG]   [BRENDA]
      Reaction: A primary alcohol + 2 cytochrome c(L) = an aldehyde + 2 reduced cytochrome c(L)
primary alcohol
 + 2 × cytochrome c(L)
 = aldehyde
 + 2 × reduced cytochrome c(L)
      Cofactor: Pyrroloquinoline quinone
Pyrroloquinoline quinone
Bound ligand (Het Group name = PQQ) corresponds exactly
Molecule diagrams generated from .mol files obtained from the KEGG ftp site
 Gene Ontology (GO) functional annotation 
  GO annot!
  Cellular component     membrane   3 terms 
  Biological process     oxidation-reduction process   3 terms 
  Biochemical function     oxidoreductase activity     5 terms  

 

 
    reference    
 
 
DOI no: 10.1006/jmbi.1996.0334 J Mol Biol 259:480-501 (1996)
PubMed id: 8676383  
 
 
Determination of the gene sequence and the three-dimensional structure at 2.4 angstroms resolution of methanol dehydrogenase from Methylophilus W3A1.
Z.Xia, W.Dai, Y.Zhang, S.A.White, G.D.Boyd, F.S.Mathews.
 
  ABSTRACT  
 
The DNA sequences for the genes encoding the heavy and light subunits of methanol dehydrogenase from Methylophilus methylotrophus W3A1 have been determined. The deduced amino acid sequence has enabled the structure of the enzyme to be refined at 2.4 angstrom resolution against X-ray data collected on a Hamlin area detector. The structure was refined using the programs PROFFT and X-PLOR with several model building step interspersed. The final model contains two heavy chains (571 amino acids), two light chains (69 amino acids), two molecules of pyrroloquinoline quinone, two Ca2+ and 521 solvent molecules. Each half molecule contains four disulfide linkages and four cis peptides. One of the disulfides is formed from two adjacent cysteine residues linked by a trans peptide which creates a novel eight-membered ring. The heavy subunit is an 8-fold beta-propeller, each "blade" of which is a four-stranded antiparallel twisted beta-sheet. The light chain is an elongated subunit stretching across the surface of the heavy subunit, with residues 1 to 32 containing four beta-turns and residues 33 to 62 forming a helix; however, it neither interacts with the active site, nor the other HL dimer and its functional role is obscure. Around the 8-fold beta-propeller there is a repeating pattern of tryptophan residues located in the outer strand of seven of the eight beta-leaflets, each packed between adjacent leaflets. Each of these tryptophan residues is centered in the beta-strand and participates in the main chain hydrogen bonding of the sheet. Five of the seven tryptophan residues have closely similar interactions with the adjacent beta-leaflet including stacking of the tryptophan indole rings against a peptide plane and formation of a hydrogen bond from NE1 of the indole ring to a main-chain carbonyl. This repeating pattern is conserved over a number of MEDH sequences. The PQQ is located on the pseudo 8-fold rotation axis of the heavy subunit, in a funnel-shaped internal cavity, sandwiched between the indole ring of Trp237 and the two sulfur atoms of the Cys103-Cys104 vicinal disulfide. A hexacoordinate Ca2+ is bound in the active site by one nitrogen and five oxygen ligands, three from the PQQ and the others from two protein side-chains. In the active site an isolated solvent molecule is bound to the O5 of PQQ and to a nearby aspartate side-chain; its position may be the binding site for methanol. The aspartate might than serve as a general base for proton abstraction from the substrate hydroxyl. The C5 atom of PQQ could be activated by electrophilic catalysis by a nearby argenine side-chain or by the calcium ion bound to PQQ.
 
  Selected figure(s)  
 
Figure 6.
Figure 6. Stereoscopic view of the H subunit of MEDH. The b-strands are shown in red and the helices are shown in blue. The PQQ and a calcium ion are shown in red. Eight four-stranded antiparallel b-sheets, labeled W1 to W8 form the base of the subunit. Several helices and two additional b-sheet structures (labeled bx and by) form a cap over the base. The PQQ is located in a funnel within the cap approximately on an 8-fold axis of pseudosymmetry. This diagram was prepared using the molecular graphics program TURBO-FRODO (Roussel & Cambillau, 1991). 		Figure 11.
Figure 11. C a diagram of the H subunit of MEDH from M. W3A1 indicating the locations of the seven conserved tryptophan side-chains on the outer strands of the four- stranded b-sheets. This diagram was prepared using the molecular graphics program TURBO-FRODO (Roussel & Cambillau, 1991).
 
  The above figures are reprinted by permission from Elsevier: J Mol Biol (1996, 259, 480-501) copyright 1996.  
  Figures were selected by an automated process.  

Literature references that cite this PDB file's key reference

  PubMed id Reference
21356200 J.Li, J.H.Gan, F.S.Mathews, and Z.X.Xia (2011).
The enzymatic reaction-induced configuration change of the prosthetic group PQQ of methanol dehydrogenase.
  Biochem Biophys Res Commun, 406, 621-626.  
21256798 Y.Hibi, K.Asai, H.Arafuka, M.Hamajima, T.Iwama, and K.Kawai (2011).
Molecular structure of La3+-induced methanol dehydrogenase-like protein in Methylobacterium radiotolerans.
  J Biosci Bioeng, 111, 547-549.  
20093290 D.S.Mern, S.W.Ha, V.Khodaverdi, N.Gliese, and H.Görisch (2010).
A complex regulatory network controls aerobic ethanol oxidation in Pseudomonas aeruginosa: indication of four levels of sensor kinases and response regulators.
  Microbiology, 156, 1505-1516.  
19224199 B.Mennenga, C.W.Kay, and H.Görisch (2009).
Quinoprotein ethanol dehydrogenase from Pseudomonas aeruginosa: the unusual disulfide ring formed by adjacent cysteine residues is essential for efficient electron transfer to cytochrome c550.
  Arch Microbiol, 191, 361-367.  
18390659 M.G.Kalyuzhnaya, K.R.Hristova, M.E.Lidstrom, and L.Chistoserdova (2008).
Characterization of a novel methanol dehydrogenase in representatives of Burkholderiales: implications for environmental detection of methylotrophy and evidence for convergent evolution.
  J Bacteriol, 190, 3817-3823.  
19111067 R.R.Thangudu, M.Manoharan, N.Srinivasan, F.Cadet, R.Sowdhamini, and B.Offmann (2008).
Analysis on conservation of disulphide bonds and their structural features in homologous protein domain families.
  BMC Struct Biol, 8, 55.  
16567634 C.W.Kay, B.Mennenga, H.Görisch, and R.Bittl (2006).
Substrate binding in quinoprotein ethanol dehydrogenase from Pseudomonas aeruginosa studied by electron-nuclear double resonance.
  Proc Natl Acad Sci U S A, 103, 5267-5272.  
16267040 C.W.Kay, B.Mennenga, H.Görisch, and R.Bittl (2006).
Structure of the pyrroloquinoline quinone radical in quinoprotein ethanol dehydrogenase.
  J Biol Chem, 281, 1470-1476.  
16632493 K.Stierand, P.C.Maass, and M.Rarey (2006).
Molecular complexes at a glance: automated generation of two-dimensional complex diagrams.
  Bioinformatics, 22, 1710-1716.  
16217027 E.I.Biterova, A.A.Turanov, V.N.Gladyshev, and J.J.Barycki (2005).
Crystal structures of oxidized and reduced mitochondrial thioredoxin reductase provide molecular details of the reaction mechanism.
  Proc Natl Acad Sci U S A, 102, 15018-15023.
PDB codes: 1zdl 1zkq
15865210 L.Wang, C.Jil, Y.Xu, J.Xu, J.Dai, Q.Wu, M.Wu, X.Zou, L.Sun, S.Gu, Y.Xie, and Y.Mao (2005).
Cloning and characterization of a novel human homolog* of mouse U26, a putative PQQ-dependent AAS dehydrogenase.
  Mol Biol Rep, 32, 47-53.  
14997549 I.Hudáky, Z.Gáspári, O.Carugo, M.Cemazar, S.Pongor, and A.Perczel (2004).
Vicinal disulfide bridge conformers by experimental methods and by ab initio and DFT molecular computations.
  Proteins, 55, 152-168.  
15273299 S.Y.Reddy, and T.C.Bruice (2004).
Determination of enzyme mechanisms by molecular dynamics: studies on quinoproteins, methanol dehydrogenase, and soluble glucose dehydrogenase.
  Protein Sci, 13, 1965-1978.  
12601748 F.S.Berven, O.A.Karlsen, J.C.Murrell, and H.B.Jensen (2003).
Multiple polypeptide forms observed in two-dimensional gels of Methylococcus capsulatus (Bath) polypeptides are generated during the separation procedure.
  Electrophoresis, 24, 757-761.  
12724517 M.Cemazar, S.Zahariev, J.J.Lopez, O.Carugo, J.A.Jones, P.J.Hore, and S.Pongor (2003).
Oxidative folding intermediates with nonnative disulfide bridges between adjacent cysteine residues.
  Proc Natl Acad Sci U S A, 100, 5754-5759.  
11714714 A.Oubrie, H.J.Rozeboom, K.H.Kalk, E.G.Huizinga, and B.W.Dijkstra (2002).
Crystal structure of quinohemoprotein alcohol dehydrogenase from Comamonas testosteroni: structural basis for substrate oxidation and electron transfer.
  J Biol Chem, 277, 3727-3732.
PDB code: 1kb0
11889098 A.S.Vangnai, D.J.Arp, and L.A.Sayavedra-Soto (2002).
Two distinct alcohol dehydrogenases participate in butane metabolism by Pseudomonas butanovora.
  J Bacteriol, 184, 1916-1924.  
11790782 L.Moise, A.Piserchio, V.J.Basus, and E.Hawrot (2002).
NMR structural analysis of alpha-bungarotoxin and its complex with the principal alpha-neurotoxin-binding sequence on the alpha 7 subunit of a neuronal nicotinic acetylcholine receptor.
  J Biol Chem, 277, 12406-12417.
PDB codes: 1kc4 1kfh 1kl8
11999397 T.Miyazaki, N.Tomiyama, M.Shinjoh, and T.Hoshino (2002).
Molecular cloning and functional expression of D-sorbitol dehydrogenase from Gluconobacter suboxydans IF03255, which requires pyrroloquinoline quinone and hydrophobic protein SldB for activity development in E. coli.
  Biosci Biotechnol Biochem, 66, 262-270.  
  12057198 Z.W.Chen, K.Matsushita, T.Yamashita, T.A.Fujii, H.Toyama, O.Adachi, H.D.Bellamy, and F.S.Mathews (2002).
Structure at 1.9 A resolution of a quinohemoprotein alcohol dehydrogenase from Pseudomonas putida HK5.
  Structure, 10, 837-849.
PDB code: 1kv9
12116408 A.Jongejan, J.A.Jongejan, and W.R.Hagen (2001).
Direct hydride transfer in the reaction mechanism of quinoprotein alcohol dehydrogenases: a quantum mechanical investigation.
  J Comput Chem, 22, 1732-1749.  
11679760 A.Oubrie, E.G.Huizinga, H.J.Rozeboom, K.H.Kalk, G.A.de Jong, J.A.Duine, and B.W.Dijkstra (2001).
Crystallization of quinohaemoprotein alcohol dehydrogenase from Comamonas testosteroni: crystals with unique optical properties.
  Acta Crystallogr D Biol Crystallogr, 57, 1732-1734.  
11761326 C.Anthony (2001).
Pyrroloquinoline quinone (PQQ) and quinoprotein enzymes.
  Antioxid Redox Signal, 3, 757-774.  
11761329 S.Fukuzumi, and S.Itoh (2001).
Catalytic control of redox reactivities of coenzyme analogs by metal ions.
  Antioxid Redox Signal, 3, 807-824.  
11149955 Y.J.Zheng, Xia Zx, Chen Zw, F.S.Mathews, and T.C.Bruice (2001).
Catalytic mechanism of quinoprotein methanol dehydrogenase: A theoretical and x-ray crystallographic investigation.
  Proc Natl Acad Sci U S A, 98, 432-434.
PDB code: 1g72
  10933491 A.Oubrie, and B.W.Dijkstra (2000).
Structural requirements of pyrroloquinoline quinone dependent enzymatic reactions.
  Protein Sci, 9, 1265-1273.  
10924133 A.R.Dewanti, and J.A.Duine (2000).
Ca2+-assisted, direct hydride transfer, and rate-determining tautomerization of C5-reduced PQQ to PQQH2, in the oxidation of beta-D-glucose by soluble, quinoprotein glucose dehydrogenase.
  Biochemistry, 39, 9384-9392.  
10655467 E.J.Neer, and T.F.Smith (2000).
A groovy new structure.
  Proc Natl Acad Sci U S A, 97, 960-962.  
10633120 M.C.Ray, P.Germon, A.Vianney, R.Portalier, and J.C.Lazzaroni (2000).
Identification by genetic suppression of Escherichia coli TolB residues important for TolB-Pal interaction.
  J Bacteriol, 182, 821-824.  
10702303 M.D.Elias, M.Tanaka, H.Izu, K.Matsushita, O.Adachi, and M.Yamada (2000).
Functions of amino acid residues in the active site of Escherichia coli pyrroloquinoline quinone-containing quinoprotein glucose dehydrogenase.
  J Biol Chem, 275, 7321-7326.  
  10673440 P.C.Bourne, M.N.Isupov, and J.A.Littlechild (2000).
The atomic-resolution structure of a novel bacterial esterase.
  Structure, 8, 143-151.
PDB code: 1qlw
10518528 A.Oubrie, H.J.Rozeboom, and B.W.Dijkstra (1999).
Active-site structure of the soluble quinoprotein glucose dehydrogenase complexed with methylhydrazine: a covalent cofactor-inhibitor complex.
  Proc Natl Acad Sci U S A, 96, 11787-11791.
PDB code: 1cru
10531500 Z.Chen, P.Baruch, F.S.Mathews, K.Matsushita, T.Yamashita, H.Toyama, and O.Adachi (1999).
Crystallization and preliminary diffraction studies of two quinoprotein alcohol dehydrogenases (ADHs): a soluble monomeric ADH from Pseudomonas putida HK5 (ADH-IIB) and a heterotrimeric membrane-bound ADH from Gluconobacter suboxydans (ADH-GS).
  Acta Crystallogr D Biol Crystallogr, 55, 1933-1936.  
9930981 Z.X.Xia, Y.N.He, W.W.Dai, S.A.White, G.D.Boyd, and F.S.Mathews (1999).
Detailed active site configuration of a new crystal form of methanol dehydrogenase from Methylophilus W3A1 at 1.9 A resolution.
  Biochemistry, 38, 1214-1220.
PDB code: 1b2n
9753475 A.J.Olsthoorn, and J.A.Duine (1998).
On the mechanism and specificity of soluble, quinoprotein glucose dehydrogenase in the oxidation of aldose sugars.
  Biochemistry, 37, 13854-13861.  
9578566 A.R.Dewanti, and J.A.Duine (1998).
Reconstitution of membrane-integrated quinoprotein glucose dehydrogenase apoenzyme with PQQ and the holoenzyme's mechanism of action.
  Biochemistry, 37, 6810-6818.  
  9914186 P.K.Mishra, and D.G.Drueckhammer (1998).
Novel cofactor derivatives and cofactor-based models.
  Curr Opin Chem Biol, 2, 758-765.  
9572874 S.Itoh, H.Kawakami, and S.Fukuzumi (1998).
Model studies on calcium-containing quinoprotein alcohol dehydrogenases. Catalytic role of Ca2+ for the oxidation of alcohols by coenzyme PQQ (4,5-dihydro-4,5-dioxo-1H-pyrrolo[2,3-f]quinoline-2, 7,9-tricarboxylic acid).
  Biochemistry, 37, 6562-6571.  
9266710 A.J.Olsthoorn, T.Otsuki, and J.A.Duine (1997).
Ca2+ and its substitutes have two different binding sites and roles in soluble, quinoprotein (pyrroloquinoline-quinone-containing) glucose dehydrogenase.
  Eur J Biochem, 247, 659-665.  
  9251208 I.R.McDonald, and J.C.Murrell (1997).
The methanol dehydrogenase structural gene mxaF and its use as a functional gene probe for methanotrophs and methylotrophs.
  Appl Environ Microbiol, 63, 3218-3224.  
8990162 T.A.Springer (1997).
Folding of the N-terminal, ligand-binding region of integrin alpha-subunits into a beta-propeller domain.
  Proc Natl Acad Sci U S A, 94, 65-72.  
9342331 Y.J.Zheng, and T.C.Bruice (1997).
Conformation of coenzyme pyrroloquinoline quinone and role of Ca2+ in the catalytic mechanism of quinoprotein methanol dehydrogenase.
  Proc Natl Acad Sci U S A, 94, 11881-11886.  
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.