PDBsum entry 1s3b

Oxidoreductase

PDB id: 1s3b

Contents

Protein chain

499 a.a. *

Ligands

FAD-RMA ×2

Waters ×819

* Residue conservation analysis

PDB id:

1s3b

Name:

Oxidoreductase

Title:

Crystal structure of maob in complex with n-methyl-n-propargyl-1(r)- aminoindan

Structure:

Amine oxidase [flavin-containing] b. Chain: a, b. Synonym: monoamine oxidase, mao-b. Engineered: yes

Source:

Homo sapiens. Human. Organism_taxid: 9606. Gene: maob. Expressed in: pichia pastoris. Expression_system_taxid: 4922.

Biol. unit:

Dimer (from PQS)

Resolution:

1.65Å R-factor: 0.204 R-free: 0.223

Authors:

C.Binda,F.Hubalek,M.Li,Y.Herzig,J.Sterling,D.E.Edmondson,A.Mattevi

Key ref:

C.Binda et al. (2004). Crystal structures of monoamine oxidase B in complex with four inhibitors of the N-propargylaminoindan class. J Med Chem, 47, 1767-1774. PubMed id: 15027868 DOI: 10.1021/jm031087c

Date:

13-Jan-04 Release date: 30-Mar-04

Protein chains

P27338  (AOFB_HUMAN) -  Amine oxidase [flavin-containing] B from Homo sapiens

Seq: 520 a.a.

Struc: 499 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

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: 10.1021/jm031087c

J Med Chem 47:1767-1774 (2004)

PubMed id: 15027868

Crystal structures of monoamine oxidase B in complex with four inhibitors of the N-propargylaminoindan class.

C.Binda, F.Hubálek, M.Li, Y.Herzig, J.Sterling, D.E.Edmondson, A.Mattevi.

ABSTRACT

Monoamine oxidase B (MAO B) is an outer mitochondrial membrane enzyme that catalyzes the oxidation of arylalkylamine neurotransmitters. The crystal structures of MAO B in complex with four of the N-propargylaminoindan class of MAO covalent inhibitors (rasagiline, N-propargyl-1(S)-aminoindan, 6-hydroxy-N-propargyl-1(R)-aminoindan, and N-methyl-N-propargyl-1(R)-aminoindan) have been determined at a resolution of better than 2.1 A. Rasagiline, 6-hydroxy-N-propargyl-1(R)-aminoindan, and N-methyl-N-propargyl-1(R)-aminoindan adopt essentially the same conformation with the extended propargyl chain covalently bound to the flavin and the indan ring located in the rear of the substrate cavity. N-Propargyl-1(S)-aminoindan binds with the indan ring in a flipped conformation with respect to the other inhibitors, which causes a slight movement of the Tyr326 side chain. Four ordered water molecules are an integral part of the active site and establish H-bond interactions to the inhibitor atoms. These structural studies may guide future drug design to improve selectivity and efficacy by introducing appropriate substituents on the rasagiline molecular scaffold.