PDBsum entry 2bxr

Oxidoreductase

PDB id: 2bxr

Contents

Protein chain

445 a.a. *

Ligands

FAD-MLG ×2

* Residue conservation analysis

PDB id:

2bxr

Name:

Oxidoreductase

Title:

Human monoamine oxidase a in complex with clorgyline, crystal form a

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:

3.00Å R-factor: 0.195 R-free: 0.238

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

Protein chains

P21397  (AOFA_HUMAN) -  Amine oxidase [flavin-containing] A from Homo sapiens

Seq: 527 a.a.

Struc: 445 a.a.

Enzyme reactions

• Enzyme class 2: E.C.1.4.3.21 - primary-amine oxidase.
• Reaction: a primary methyl amine + O2 + H2O = an aldehyde + H2O2 + NH4⁺
• Enzyme class 3: E.C.1.4.3.4 - monoamine oxidase.
• Reaction: a secondary aliphatic amine + O2 + H2O = a primary amine + an aldehyde + H2O2
• Cofactor: FAD

FAD (Bound ligand (Het Group name = FAD) corresponds exactly)

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

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.