2xfu: Difference between revisions

==HUMAN MONOAMINE OXIDASE B WITH TRANYLCYPROMINE==

<StructureSection load='2xfu' size='340' side='right' caption='[[2xfu]], [[Resolution|resolution]] 2.20&Aring;' scene=''>

<table><tr><td colspan='2'>[[2xfu]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. This structure supersedes the now removed PDB entry [http://oca.weizmann.ac.il/oca-bin/send-pdb?obs=1&id=1ojb 1ojb]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2XFU OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2XFU FirstGlance]. <br>

</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=3PL:3-PHENYLPROPANAL'>3PL</scene>, <scene name='pdbligand=FA8:[[(2R,3S,4S)-5-[(4AS)-7,8-DIMETHYL-2,4-DIOXO-4A,5-DIHYDROBENZO[G]PTERIDIN-10-YL]-2,3,4-TRIHYDROXY-PENTOXY]-HYDROXY-PHOSPHORYL]+[(2R,3S,4R,5R)-5-(6-AMINOPURIN-9-YL)-3,4-DIHYDROXY-OXOLAN-2-YL]METHYL+HYDROGEN+PHOSPHATE'>FA8</scene></td></tr>

<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Monoamine_oxidase Monoamine oxidase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=1.4.3.4 1.4.3.4] </span></td></tr>

<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2xfu FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2xfu OCA], [http://www.rcsb.org/pdb/explore.do?structureId=2xfu RCSB], [http://www.ebi.ac.uk/pdbsum/2xfu PDBsum]</span></td></tr>

[[http://www.uniprot.org/uniprot/AOFB_HUMAN AOFB_HUMAN]] Catalyzes the oxidative deamination of biogenic and xenobiotic amines and has important functions in the metabolism of neuroactive and vasoactive amines in the central nervous system and peripheral tissues. MAOB preferentially degrades benzylamine and phenylethylamine.  

     <scriptWhenChecked>select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/xf/2xfu_consurf.spt"</scriptWhenChecked>

</jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/chain_selection.php?pdb_ID=2ata ConSurf].

Monoamine oxidase B (MAO-B) is an outer mitochondrial membrane-bound enzyme that catalyzes the oxidative deamination of arylalkylamine neurotransmitters and has been a target for a number of clinically used drug inhibitors. The 1.7-A structure of the reversible isatin-MAO-B complex has been determined; it forms a basis for the interpretation of the enzyme's structure when bound to either reversible or irreversible inhibitors. 1,4-Diphenyl-2-butene is found to be a reversible MAO-B inhibitor, which occupies both the entrance and substrate cavity space in the enzyme. Comparison of these two structures identifies Ile-199 as a "gate" between the two cavities. Rotation of the side chain allows for either separation or fusion of the two cavities. Inhibition of the enzyme with N-(2-aminoethyl)-p-chlorobenzamide results in the formation of a covalent N(5) flavin adduct with the phenyl ring of the inhibitor occupying a position in the catalytic site overlapping that of isatin. Inhibition of MAO-B with the clinically used trans-2-phenylcyclopropylamine results in the formation of a covalent C(4a) flavin adduct with an opened cyclopropyl ring and the phenyl ring in a parallel orientation to the flavin. The peptide bond between the flavin-substituted Cys-397 and Tyr-398 is in a cis conformation, which allows the proper orientation of the phenolic ring of Tyr-398 in the active site. The flavin ring exists in a twisted nonplanar conformation, which is observed in the oxidized form as well as in both the N(5) and the C(4a) adducts. An immobile water molecule is H-bonded to Lys-296 and to the N(5) of the flavin as observed in other flavin-dependent amine oxidases. The active site cavities are highly apolar; however, hydrophilic areas exist near the flavin and direct the amine moiety of the substrate for binding and catalysis. Small conformational changes are observed on comparison of the different inhibitor-enzyme complexes. Future MAO-B drug design will need to consider "induced fit" contributions as an element in ligand-enzyme interactions.

Insights into the mode of inhibition of human mitochondrial monoamine oxidase B from high-resolution crystal structures.,Binda C, Li M, Hubalek F, Restelli N, Edmondson DE, Mattevi A Proc Natl Acad Sci U S A. 2003 Aug 19;100(17):9750-5. Epub 2003 Aug 11. PMID:12913124<ref>PMID:12913124</ref>

[[Category: Monoamine oxidase]]

[[Category: Binda, C]]

[[Category: Edmondson, D E]]

[[Category: Hubalek, F]]

[[Category: Li, M]]

[[Category: Mattevi, A]]

[[Category: Restelli, N]]

[[Category: Oxidoreductase]]