3zyx | pdb_00003zyx

CRYSTAL STRUCTURE OF HUMAN MONOAMINE OXIDASE B IN COMPLEX WITH METHYLENE BLUE AND BEARING THE DOUBLE MUTATION I199A-Y326A

spinqualitylabelsall models 3zyx, resolution 2.20Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 3zyx is a 2 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Ligands: FAD, MBT Related: 2c67, 1s3e, 2c73, 2v60, 1oj9, 2vz2, 1ojd, 1s3b, 2c66, 2xfo, 2bk5, 1h8r, 2c70, 2xfn, 2bk3, 2c76, 2vrl, 1oja, 2v5z, 2xfu, 2byb, 2vrm, 2c65, 2c64, 2xcg, 2xfp, 2bk4, 2c75, 2v61, 1s2y, 2c72, 1gos, 1s2q, 2xfq, 1ojc Activity: Monoamine oxidase, with EC number 1.4.3.4 Resources: FirstGlance, OCA, RCSB, PDBsum Publication Abstract from PubMed The major structural difference between human monoamine oxidases A (MAO A) and B (MAO B) is that MAO A has a monopartite substrate cavity of approximately 550 A(3) volume and MAO B contains a dipartite cavity structure with volumes of approximately 290 A(3) (entrance cavity) and approximately 400 A(3) (substrate cavity). Ile199 and Tyr326 side chains separate these two cavities in MAO B. To probe the function of these gating residues, Ile199Ala and Ile199Ala-Tyr326Ala mutant forms of MAO B were investigated. Structural data on the Ile199Ala MAO B mutant show no alterations in active site geometries compared with wild-type enzyme while the Ile199Ala-Tyr326Ala MAO B mutant exhibits alterations in residues 100-103 which are part of the loop gating the entrance to the active site. Both mutant enzymes exhibit catalytic properties with increased amine K(M) but unaltered k(cat) values. The altered K(M) values on mutation are attributed to the influence of the cavity structure in the binding and subsequent deprotonation of the amine substrate. Both mutant enzymes exhibit weaker binding affinities relative to wild-type enzyme for small reversible inhibitors. Ile199Ala MAO B exhibits an increase in binding affinity for reversible MAO B specific inhibitors which bridge both cavities. The Ile199Ala-Tyr326Ala double mutant exhibits inhibitor binding properties more similar to those of MAO A than to MAO B. These results demonstrate that the bipartite cavity structure in MAO B plays an important role in substrate and inhibitor recognition to distinguish its specificities from those of MAO A and provide insights into specific reversible inhibitor design for these membrane-bound enzymes. Database The atomic coordinates and structural factors of the structure of human MAO B Ile199Ala-Tyr326Ala double mutant have been deposited in the Protein Data Bank under the accession number 3zyx. The 'gating' residues Ile199 and Tyr326 in human monoamine oxidase B function in substrate and inhibitor recognition.,Milczek EM, Binda C, Rovida S, Mattevi A, Edmondson DE FEBS J. 2011 Dec;278(24):4860-9. doi: 10.1111/j.1742-4658.2011.08386.x., Epub 2011 Nov 3. PMID:21978362 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also Monoamine oxidase

Proteopedia Page Contributors and Editors (what is this?)

OCA