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PDBsum entry 2bxs

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Oxidoreductase PDB id
2bxs
Jmol
Contents
Protein chain
490 a.a. *
Ligands
FAD-MLG ×2
* Residue conservation analysis
PDB id:
2bxs
Name: Oxidoreductase
Title: Human monoamine oxidase a in complex with clorgyline, crystal form b
Structure: Amine oxidase [flavin-containing] a. Chain: a, b. Synonym: monoamine oxidase type a, mao-a. Engineered: yes
Source: Homo sapiens. Human. Organism_taxid: 9606. Expressed in: pichia pastoris. Expression_system_taxid: 4922
Resolution:
3.15Å     R-factor:   0.271     R-free:   0.330
Authors: L.De Colibus,C.Binda,D.E.Edmondson,A.Mattevi
Key ref:
L.De Colibus et al. (2005). Three-dimensional structure of human monoamine oxidase A (MAO A): relation to the structures of rat MAO A and human MAO B. Proc Natl Acad Sci U S A, 102, 12684-12689. PubMed id: 16129825 DOI: 10.1073/pnas.0505975102
Date:
27-Jul-05     Release date:   09-Aug-05    
PROCHECK
Go to PROCHECK summary
 Headers
 References

Protein chains
Pfam   ArchSchema ?
P21397  (AOFA_HUMAN) -  Amine oxidase [flavin-containing] A
Seq:
Struc:
 
Seq:
Struc:
527 a.a.
490 a.a.
Key:    PfamA domain  PfamB domain  Secondary structure  CATH domain

 Enzyme reactions 
   Enzyme class: E.C.1.4.3.4  - Monoamine oxidase.
[IntEnz]   [ExPASy]   [KEGG]   [BRENDA]
      Reaction: RCH2NHR' + H2O + O2 = RCHO + R'NH2 + H2O2
RCH(2)NHR'
+ H(2)O
+ O(2)
= RCHO
+ R'NH(2)
+ H(2)O(2)
      Cofactor: FAD
FAD
Bound ligand (Het Group name = FAD) corresponds exactly
Molecule diagrams generated from .mol files obtained from the KEGG ftp site
 Gene Ontology (GO) functional annotation 
  GO annot!
  Cellular component     membrane   4 terms 
  Biological process     small molecule metabolic process   10 terms 
  Biochemical function     oxidoreductase activity     2 terms  

 

 
    reference    
 
 
DOI no: 10.1073/pnas.0505975102 Proc Natl Acad Sci U S A 102:12684-12689 (2005)
PubMed id: 16129825  
 
 
Three-dimensional structure of human monoamine oxidase A (MAO A): relation to the structures of rat MAO A and human MAO B.
L.De Colibus, M.Li, C.Binda, A.Lustig, D.E.Edmondson, A.Mattevi.
 
  ABSTRACT  
 
The three-dimensional structure of recombinant human monoamine oxidase A (hMAO A) as its clorgyline-inhibited adduct is described. Although the chain-fold of hMAO A is similar to that of rat MAO A and human MAO B (hMAO B), hMAO A is unique in that it crystallizes as a monomer and exhibits the solution hydrodynamic behavior of a monomeric form rather than the dimeric form of hMAO B and rat MAO A. hMAO A's active site consists of a single hydrophobic cavity of approximately 550 A3, which is smaller than that determined from the structure of deprenyl-inhibited hMAO B (approximately 700 A3) but larger than that of rat MAO A (approximately 450 A3). An important component of the active site structure of hMAO A is the loop conformation of residues 210-216, which differs from that of hMAO B and rat MAO A. The origin of this structural alteration is suggested to result from long-range interactions in the monomeric form of the enzyme. In addition to serving as a basis for the development of hMAO A specific inhibitors, these data support the proposal that hMAO A involves a change from the dimeric to the monomeric form through a Glu-151 --> Lys mutation that is specific of hMAO A [Andrès, A. M., Soldevila, M., Navarro, A., Kidd, K. K., Oliva, B. & Bertranpetit, J. (2004) Hum. Genet. 115, 377-386]. These considerations put into question the use of MAO A from nonhuman sources in drug development for use in humans.
 
  Selected figure(s)  
 
Figure 3.
Fig. 3. Stereo closed-up view of the clorgyline site in hMAO A. Atom colors are as in Fig. 1. The backbone trace of loop 210-216 is shown as a coil.
Figure 5.
Fig. 5. Active site cavities in hMAO A and hMAO B. (A) The surface of active site cavity in hMAO A is shown in red chicken-wire representation in the same orientation as in Fig. 3. Clorgyline is depicted in black. (B) Active site comparison of hMAO A and hMAO B with the crucial Phe-208 and Ile-335 residues of hMAO A superimposed to the corresponding Ile-199 and Tyr-326 residues of hMAO B. The protein and inhibitor atoms of hMAO B are in red. With respect to A, the model has been rotated by 90° around the vertical axis in the plane of the drawing. (C) The active site cavity (red surface) of hMAO B in complex with deprenyl (black) is depicted in the same orientation as in A.
 
  Figures were selected by an automated process.  

Literature references that cite this PDB file's key reference

  PubMed id Reference
21383134 G.Kachalova, K.Decker, A.Holt, and H.D.Bartunik (2011).
Crystallographic snapshots of the complete reaction cycle of nicotine degradation by an amine oxidase of the monoamine oxidase (MAO) family.
  Proc Natl Acad Sci U S A, 108, 4800-4805.  
21354322 M.Aldeco, B.K.Arslan, and D.E.Edmondson (2011).
Catalytic and inhibitor binding properties of zebrafish monoamine oxidase (zMAO): comparisons with human MAO A and MAO B.
  Comp Biochem Physiol B Biochem Mol Biol, 159, 78-83.  
19890267 J.S.Fowler, J.Logan, A.J.Azzaro, R.M.Fielding, W.Zhu, A.K.Poshusta, D.Burch, B.Brand, J.Free, M.Asgharnejad, G.J.Wang, F.Telang, B.Hubbard, M.Jayne, P.King, P.Carter, S.Carter, Y.Xu, C.Shea, L.Muench, D.Alexoff, E.Shumay, M.Schueller, D.Warner, and K.Apelskog-Torres (2010).
Reversible inhibitors of monoamine oxidase-A (RIMAs): robust, reversible inhibition of human brain MAO-A by CX157.
  Neuropsychopharmacology, 35, 623-631.  
19883764 J.Wang, and D.E.Edmondson (2010).
High-level expression and purification of rat monoamine oxidase A (MAO A) in Pichia pastoris: comparison with human MAO A.
  Protein Expr Purif, 70, 211-217.  
19634988 M.A.Wouters, S.W.Fan, and N.L.Haworth (2010).
Disulfides as redox switches: from molecular mechanisms to functional significance.
  Antioxid Redox Signal, 12, 53-91.  
19651103 P.F.Fitzpatrick (2010).
Oxidation of amines by flavoproteins.
  Arch Biochem Biophys, 493, 13-25.  
20410615 Z.Jia, S.Wei, and Q.Zhu (2010).
Monoamine oxidase inhibitors: benzylidene-prop-2-ynyl-amines analogues.
  Biol Pharm Bull, 33, 725-728.  
19296688 A.K.Upadhyay, and D.E.Edmondson (2009).
Development of spin-labeled pargyline analogues as specific inhibitors of human monoamine oxidases A and B.
  Biochemistry, 48, 3928-3935.  
19371079 D.E.Edmondson, C.Binda, J.Wang, A.K.Upadhyay, and A.Mattevi (2009).
Molecular and mechanistic properties of the membrane-bound mitochondrial monoamine oxidases.
  Biochemistry, 48, 4220-4230.  
19624733 F.Forneris, E.Battaglioli, A.Mattevi, and C.Binda (2009).
New roles of flavoproteins in molecular cell biology: histone demethylase LSD1 and chromatin.
  FEBS J, 276, 4304-4312.  
19645722 J.Wang, J.Harris, D.D.Mousseau, and D.E.Edmondson (2009).
Mutagenic probes of the role of Ser209 on the cavity shaping loop of human monoamine oxidase A.
  FEBS J, 276, 4569-4581.  
19673610 M.Naoi, and W.Maruyama (2009).
Functional mechanism of neuroprotection by inhibitors of type B monoamine oxidase in Parkinson's disease.
  Expert Rev Neurother, 9, 1233-1250.  
18424170 A.K.Upadhyay, and D.E.Edmondson (2008).
Characterization of detergent purified recombinant rat liver monoamine oxidase B expressed in Pichia pastoris.
  Protein Expr Purif, 59, 349-356.  
18418249 A.L.Scott, M.Bortolato, K.Chen, and J.C.Shih (2008).
Novel monoamine oxidase A knock out mice with human-like spontaneous mutation.
  Neuroreport, 19, 739-743.  
18757736 E.Akiva, Z.Itzhaki, and H.Margalit (2008).
Built-in loops allow versatility in domain-domain interactions: lessons from self-interacting domains.
  Proc Natl Acad Sci U S A, 105, 13292-13297.  
18674618 E.P.Carpenter, K.Beis, A.D.Cameron, and S.Iwata (2008).
Overcoming the challenges of membrane protein crystallography.
  Curr Opin Struct Biol, 18, 581-586.  
18183391 E.W.van Hellemond, M.van Dijk, D.P.Heuts, D.B.Janssen, and M.W.Fraaije (2008).
Discovery and characterization of a putrescine oxidase from Rhodococcus erythropolis NCIMB 11540.
  Appl Microbiol Biotechnol, 78, 455-463.  
  18323603 K.E.Atkin, R.Reiss, N.J.Turner, A.M.Brzozowski, and G.Grogan (2008).
Cloning, expression, purification, crystallization and preliminary X-ray diffraction analysis of variants of monoamine oxidase from Aspergillus niger.
  Acta Crystallogr Sect F Struct Biol Cryst Commun, 64, 182-185.  
18391214 S.Y.Son, J.Ma, Y.Kondou, M.Yoshimura, E.Yamashita, and T.Tsukihara (2008).
Structure of human monoamine oxidase A at 2.2-A resolution: the control of opening the entry for substrates/inhibitors.
  Proc Natl Acad Sci U S A, 105, 5739-5744.
PDB codes: 2z5x 2z5y
17521909 A.Fierro, M.Osorio-Olivares, B.K.Cassels, D.E.Edmondson, S.Sepúlveda-Boza, and M.Reyes-Parada (2007).
Human and rat monoamine oxidase-A are differentially inhibited by (S)-4-alkylthioamphetamine derivatives: insights from molecular modeling studies.
  Bioorg Med Chem, 15, 5198-5206.  
17573034 D.E.Edmondson, C.Binda, and A.Mattevi (2007).
Structural insights into the mechanism of amine oxidation by monoamine oxidases A and B.
  Arch Biochem Biophys, 464, 269-276.  
17393064 D.E.Edmondson, L.DeColibus, C.Binda, M.Li, and A.Mattevi (2007).
New insights into the structures and functions of human monoamine oxidases A and B.
  J Neural Transm, 114, 703-705.  
17393065 F.Cruz, and D.E.Edmondson (2007).
Kinetic properties of recombinant MAO-A on incorporation into phospholipid nanodisks.
  J Neural Transm, 114, 699-702.  
17401534 J.Wang, and D.E.Edmondson (2007).
Do monomeric vs dimeric forms of MAO-A make a difference? A direct comparison of the catalytic properties of rat and human MAO-A's.
  J Neural Transm, 114, 721-724.  
17401533 K.Yelekçi, O.Karahan, and M.Toprakçi (2007).
Docking of novel reversible monoamine oxidase-B inhibitors: efficient prediction of ligand binding sites and estimation of inhibitors thermodynamic properties.
  J Neural Transm, 114, 725-732.  
17401536 M.A.Akyüz, S.S.Erdem, and D.E.Edmondson (2007).
The aromatic cage in the active site of monoamine oxidase B: effect on the structural and electronic properties of bound benzylamine and p-nitrobenzylamine.
  J Neural Transm, 114, 693-698.  
17721552 R.R.Ramsay, C.Dunford, and P.K.Gillman (2007).
Methylene blue and serotonin toxicity: inhibition of monoamine oxidase A (MAO A) confirms a theoretical prediction.
  Br J Pharmacol, 152, 946-951.  
17193252 A.Carotti, C.Altomare, M.Catto, C.Gnerre, L.Summo, A.De Marco, S.Rose, P.Jenner, and B.Testa (2006).
Lipophilicity plays a major role in modulating the inhibition of monoamine oxidase B by 7-substituted coumarins.
  Chem Biodivers, 3, 134-149.  
16689938 C.B.Chiribau, M.Mihasan, P.Ganas, G.L.Igloi, V.Artenie, and R.Brandsch (2006).
Final steps in the catabolism of nicotine.
  FEBS J, 273, 1528-1536.  
16611214 F.Chimenti, A.Bolasco, F.Manna, D.Secci, P.Chimenti, A.Granese, O.Befani, P.Turini, S.Alcaro, and F.Ortuso (2006).
Synthesis and molecular modelling of novel substituted-4,5-dihydro-(1H)-pyrazole derivatives as potent and highly selective monoamine oxidase-A inhibitors.
  Chem Biol Drug Des, 67, 206-214.  
17229101 K.Guillem, C.Vouillac, M.R.Azar, L.H.Parsons, G.F.Koob, M.Cador, and L.Stinus (2006).
Monoamine oxidase A rather than monoamine oxidase B inhibition increases nicotine reinforcement in rats.
  Eur J Neurosci, 24, 3532-3540.  
17070680 L.De Colibus, and A.Mattevi (2006).
New frontiers in structural flavoenzymology.
  Curr Opin Struct Biol, 16, 722-728.  
16552415 M.B.Youdim, D.Edmondson, and K.F.Tipton (2006).
The therapeutic potential of monoamine oxidase inhibitors.
  Nat Rev Neurosci, 7, 295-309.  
16732136 S.H.Preskorn (2006).
Why the transdermal delivery of selegiline (6 mg/24 hr) obviates the need for a dietary restriction on tyramine.
  J Psychiatr Pract, 12, 168-172.  
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.