spacer
spacer

PDBsum entry 1o5w

Go to PDB code: 
protein ligands Protein-protein interface(s) links
Oxidoreductase PDB id
1o5w
Jmol
Contents
Protein chains
511 a.a. *
Ligands
FAD-MLG ×4
* Residue conservation analysis
PDB id:
1o5w
Name: Oxidoreductase
Title: The structure basis of specific recognitions for substrates and inhibitors of rat monoamine oxidase a
Structure: Amine oxidase [flavin-containing] a. Chain: a, b, c, d. Synonym: monoamine oxidase, mao-a. Engineered: yes
Source: Rattus norvegicus. Norway rat. Organism_taxid: 10116. Expressed in: saccharomyces cerevisiae. Expression_system_taxid: 4932.
Biol. unit: Dimer (from PQS)
Resolution:
3.20Å     R-factor:   0.220     R-free:   0.282
Authors: J.Ma,M.Yoshimura,E.Yamashita,A.Nakagawa,A.Ito,T.Tsukihara
Key ref:
J.Ma et al. (2004). Structure of rat monoamine oxidase A and its specific recognitions for substrates and inhibitors. J Mol Biol, 338, 103-114. PubMed id: 15050826 DOI: 10.1016/j.jmb.2004.02.032
Date:
06-Oct-03     Release date:   20-Apr-04    
PROCHECK
Go to PROCHECK summary
 Headers
 References

Protein chains
Pfam   ArchSchema ?
P21396  (AOFA_RAT) -  Amine oxidase [flavin-containing] A
Seq:
Struc:
 
Seq:
Struc:
526 a.a.
511 a.a.*
Key:    PfamA domain  PfamB domain  Secondary structure  CATH domain
* PDB and UniProt seqs differ at 3 residue positions (black crosses)

 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     oxidation-reduction process   6 terms 
  Biochemical function     oxidoreductase activity     4 terms  

 

 
    reference    
 
 
DOI no: 10.1016/j.jmb.2004.02.032 J Mol Biol 338:103-114 (2004)
PubMed id: 15050826  
 
 
Structure of rat monoamine oxidase A and its specific recognitions for substrates and inhibitors.
J.Ma, M.Yoshimura, E.Yamashita, A.Nakagawa, A.Ito, T.Tsukihara.
 
  ABSTRACT  
 
Monoamine oxidase (MAO), a mitochondrial outer membrane enzyme, catalyzes the degradation of neurotransmitters in the central nervous system and is the target for anti-depression drug design. Two subtypes of MAO, MAOA and MAOB, are similar in primary sequences but have unique substrate and inhibitor specificities. The structures of human MAOB complexed with various inhibitors were reported early. To understand the mechanisms of specific substrate and inhibitor recognitions of MAOA and MAOB, we have determined the crystal structure of rat MAOA complexed with the specific inhibitor, clorgyline, at 3.2A resolution. The comparison of the structures between MAOA and MAOB clearly explains the specificity of clorgyline for MAOA inhibition. The fitting of serotonin into the binding pockets of MAOs demonstrates that MAOB Tyr326 would block access of the 5-hydroxy group of serotonin into the enzyme. These results will lead to further understanding of the MAOA function and to new anti-depression drug design. This study also presents that MAOA has a transmembrane helix at the C-terminal region. This is the first crystal structure of membrane protein with an isolated transmembrane helix.
 
  Selected figure(s)  
 
Figure 8.
Figure 8. Inhibitor and substrate-binding models in MAOA and MAOB. Figures were produced by same method as for Figure 7. MAOB residues are shown as semi-transparent. (a) Inhibitors of MAOB are superposed on clorgyline in the active center of MAOA. The colors used to discriminate the different inhibitors are red for clorgyline, cyan for pargyline (from 1GOS), green for 1,4-diphenyl-2-butene (from PDB code 1OJ9), blue for isatin (from PDB code 1OJA), purple for tranylcypromine (from PDB code 1OJB), and orange for N-(2-aminoethyl)-p-chlorobenzamide (from PDB code 1OJC). (b) 5-HT is built into the active center of MAOA and is shown as a ball-and-stick model.
Figure 9.
Figure 9. Postulated membrane-binding regions of MAOA. (a) Membrane-binding model of MAOA. The C-terminal structure of molecule D is calculated according to the molecule C to show a sound CD dimer structure of MAOA. The molecule D is shown in transparent mode. Positively charged residues that are postulated to interact with membrane surfaces in molecule C are shown in ball-and-stick model. The mitochondrial outer membrane surfaces are indicated by two continuous lines. (b) stereo view of the detailed structure of membrane-binding regions of molecule C of MAOA. The orientation is the same as that of (a). Tryptophan and tyrosine residues are labeled.
 
  The above figures are reprinted by permission from Elsevier: J Mol Biol (2004, 338, 103-114) copyright 2004.  
  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.
PDB code: 3ng7
21397504 S.M.Shelke, S.H.Bhosale, R.C.Dash, M.R.Suryawanshi, and K.R.Mahadik (2011).
Exploration of new scaffolds as potential MAO-A inhibitors using pharmacophore and 3D-QSAR based in silico screening.
  Bioorg Med Chem Lett, 21, 2419-2424.  
20196071 G.Kefala, C.Ahn, M.Krupa, L.Esquivies, I.Maslennikov, W.Kwiatkowski, and S.Choe (2010).
Structures of the OmpF porin crystallized in the presence of foscholine-12.
  Protein Sci, 19, 1117-1125.
PDB codes: 3k19 3k1b
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.  
20204405 V.Flamand, H.Zhao, and D.M.Peehl (2010).
Targeting monoamine oxidase A in advanced prostate cancer.
  J Cancer Res Clin Oncol, 136, 1761-1771.  
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.  
19408960 H.Gaweska, M.Henderson Pozzi, D.M.Schmidt, D.G.McCafferty, and P.F.Fitzpatrick (2009).
Use of pH and kinetic isotope effects to establish chemistry as rate-limiting in oxidation of a peptide substrate by LSD1.
  Biochemistry, 48, 5440-5445.  
19199575 M.Henderson Pozzi, V.Gawandi, and P.F.Fitzpatrick (2009).
pH dependence of a mammalian polyamine oxidase: insights into substrate specificity and the role of lysine 315.
  Biochemistry, 48, 1508-1516.  
19243237 T.Senda, M.Senda, S.Kimura, and T.Ishida (2009).
Redox control of protein conformation in flavoproteins.
  Antioxid Redox Signal, 11, 1741-1766.  
19650872 X.Cao, L.Rui, P.R.Pennington, J.Chlan-Fourney, Z.Jiang, Z.Wei, X.M.Li, D.E.Edmondson, and D.D.Mousseau (2009).
Serine 209 resides within a putative p38(MAPK) consensus motif and regulates monoamine oxidase-A activity.
  J Neurochem, 111, 101-110.  
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.  
18391190 E.R.Geertsma, M.Groeneveld, D.J.Slotboom, and B.Poolman (2008).
Quality control of overexpressed membrane proteins.
  Proc Natl Acad Sci U S A, 105, 5722-5727.  
  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.  
18652859 M.Bortolato, K.Chen, and J.C.Shih (2008).
Monoamine oxidase inactivation: from pathophysiology to therapeutics.
  Adv Drug Deliv Rev, 60, 1527-1533.  
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.  
17603894 A.L.Lomize, I.D.Pogozheva, M.A.Lomize, and H.I.Mosberg (2007).
The role of hydrophobic interactions in positioning of peripheral proteins in membranes.
  BMC Struct Biol, 7, 44.  
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.  
17551828 J.C.Shih (2007).
Monoamine oxidases: from tissue homogenates to transgenic mice.
  Neurochem Res, 32, 1757-1761.  
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.  
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.  
17385067 S.G.Sunal, S.Yabanoglu, A.Yesilada, and G.Ucar (2007).
Monoamine oxidase inhibitory activities of novel 3,4-dihydroquinolin-(1H)-2-one derivatives.
  J Neural Transm, 114, 717-719.  
16458520 A.A.Khalil, B.Davies, and N.Castagnoli (2006).
Isolation and characterization of a monoamine oxidase B selective inhibitor from tobacco smoke.
  Bioorg Med Chem, 14, 3392-3398.  
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.  
16462816 B.Bondy, A.Buettner, and P.Zill (2006).
Genetics of suicide.
  Mol Psychiatry, 11, 336-351.  
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.  
16421512 M.Morishima, N.Harada, S.Hara, A.Sano, H.Seno, A.Takahashi, Y.Morita, and Y.Nakaya (2006).
Monoamine oxidase A activity and norepinephrine level in hippocampus determine hyperwheel running in SPORTS rats.
  Neuropsychopharmacology, 31, 2627-2638.  
16467939 S.S.Erdem, O.Karahan, I.Yildiz, and K.Yelekçi (2006).
A computational study on the amine-oxidation mechanism of monoamine oxidase: insight into the polar nucleophilic mechanism.
  Org Biomol Chem, 4, 646-658.  
15710600 F.Hubálek, C.Binda, A.Khalil, M.Li, A.Mattevi, N.Castagnoli, and D.E.Edmondson (2005).
Demonstration of isoleucine 199 as a structural determinant for the selective inhibition of human monoamine oxidase B by specific reversible inhibitors.
  J Biol Chem, 280, 15761-15766.
PDB codes: 2bk3 2bk4 2bk5
16129825 L.De Colibus, M.Li, C.Binda, A.Lustig, D.E.Edmondson, and A.Mattevi (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.
PDB codes: 2bxr 2bxs 2byb
15556933 S.E.Rigby, R.M.Hynson, R.R.Ramsay, A.W.Munro, and N.S.Scrutton (2005).
A stable tyrosyl radical in monoamine oxidase A.
  J Biol Chem, 280, 4627-4631.  
15223314 Z.Yang, L.Shipman, M.Zhang, B.P.Anton, R.J.Roberts, and X.Cheng (2004).
Structural characterization and comparative phylogenetic analysis of Escherichia coli HemK, a protein (N5)-glutamine methyltransferase.
  J Mol Biol, 340, 695-706.
PDB code: 1t43
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.