2BYB

Human Monoamine Oxidase B in complex with Deprenyl

Summary for 2BYB

• Entry DOI: 10.2210/pdb2byb/pdb
• Related: 1GOS 1H8R 1OJ9 1OJA 1OJB 1OJC 1OJD 1S2Q 1S2Y 1S3B 1S3E 2BK3 2BK4 2BK5
• Descriptor: AMINE OXIDASE [FLAVIN-CONTAINING] B, FLAVIN-ADENINE DINUCLEOTIDE, DEPRENYL, ... (4 entities in total)
• Functional Keywords: oxidoreductase, fad-containing amine oxidase, maob acetylation, fad, flavoprotein, maob, transmembrane neurotransmitter, membrane-protein
• Biological source: HOMO SAPIENS (HUMAN)
• Cellular location: Mitochondrion outer membrane; Single-pass type IV membrane protein; Cytoplasmic side: P27338
• Total number of polymer chains: 2
• Total formula weight: 119625.15

Authors

Binda, C.,De Colibus, L.,Edmondson, D.E.,Mattevi, A. (deposition date: 2005-07-29, release date: 2005-08-09, Last modification date: 2024-10-23)

Primary citation

De Colibus, L.,Li, M.,Binda, C.,Lustig, A.,Edmondson, D.E.,Mattevi, A.
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.USA, 102:12864-, 2005

PubMed 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.

PubMed: 16129825
DOI: 10.1073/PNAS.0505975102

Experimental method

X-RAY DIFFRACTION (2.2 Å)