Crystal structure of human monoamine oxidase B, a drug target enzyme monotopically inserted into the mitochondrial outer membrane

Claudia Binda, Frantisek Hubálek, Min Li, Dale E. Edmondson, Andrea Mattevi

Research output: Contribution to journalArticle

Abstract

Monoamine oxidase B (MAO B) is an outer mitochondrial membrane protein that oxidizes arylalkylamine neurotransmitters and has been a valuable drug target for many neurological disorders. The 1.7 Å resolution structure of human MAO B shows the enzyme is dimeric with a C-terminal transmembrane helix protruding from each monomer and anchoring the protein to the membrane. This helix departs perpendicularly from the base of the structure in a different way with respect to other monotopic membrane proteins. Several apolar loops exposed on the protein surface are located in proximity of the C-terminal helix, providing additional membrane-binding interactions. One of these loops (residues 99-112) also functions in opening and closing the MAO B active site cavity, which suggests that the membrane may have a role in controlling substrate binding.

Original languageEnglish (US)
Pages (from-to)225-228
Number of pages4
JournalFEBS Letters
Volume564
Issue number3
DOIs
StatePublished - Apr 30 2004
Externally publishedYes

Fingerprint

Monoamine Oxidase
Mitochondrial Membranes
Membrane Proteins
Crystal structure
Membranes
Enzymes
Pharmaceutical Preparations
Neurotransmitter Agents
Mitochondrial Proteins
Monomers
Nervous System Diseases
Catalytic Domain
Substrates
Proteins

Keywords

  • Flavin
  • Human monoamine oxidase B structure
  • MAO, monoamine oxidase
  • Mitochondrial membrane
  • Monotopic

ASJC Scopus subject areas

  • Biochemistry
  • Biophysics
  • Molecular Biology

Cite this

Crystal structure of human monoamine oxidase B, a drug target enzyme monotopically inserted into the mitochondrial outer membrane. / Binda, Claudia; Hubálek, Frantisek; Li, Min; Edmondson, Dale E.; Mattevi, Andrea.

In: FEBS Letters, Vol. 564, No. 3, 30.04.2004, p. 225-228.

Research output: Contribution to journalArticle

Binda, Claudia ; Hubálek, Frantisek ; Li, Min ; Edmondson, Dale E. ; Mattevi, Andrea. / Crystal structure of human monoamine oxidase B, a drug target enzyme monotopically inserted into the mitochondrial outer membrane. In: FEBS Letters. 2004 ; Vol. 564, No. 3. pp. 225-228.
@article{ab25d110e88a48078ed3d13c079f7218,
title = "Crystal structure of human monoamine oxidase B, a drug target enzyme monotopically inserted into the mitochondrial outer membrane",
abstract = "Monoamine oxidase B (MAO B) is an outer mitochondrial membrane protein that oxidizes arylalkylamine neurotransmitters and has been a valuable drug target for many neurological disorders. The 1.7 {\AA} resolution structure of human MAO B shows the enzyme is dimeric with a C-terminal transmembrane helix protruding from each monomer and anchoring the protein to the membrane. This helix departs perpendicularly from the base of the structure in a different way with respect to other monotopic membrane proteins. Several apolar loops exposed on the protein surface are located in proximity of the C-terminal helix, providing additional membrane-binding interactions. One of these loops (residues 99-112) also functions in opening and closing the MAO B active site cavity, which suggests that the membrane may have a role in controlling substrate binding.",
keywords = "Flavin, Human monoamine oxidase B structure, MAO, monoamine oxidase, Mitochondrial membrane, Monotopic",
author = "Claudia Binda and Frantisek Hub{\'a}lek and Min Li and Edmondson, {Dale E.} and Andrea Mattevi",
year = "2004",
month = "4",
day = "30",
doi = "10.1016/S0014-5793(04)00209-1",
language = "English (US)",
volume = "564",
pages = "225--228",
journal = "FEBS Letters",
issn = "0014-5793",
publisher = "Elsevier",
number = "3",

}

TY - JOUR

T1 - Crystal structure of human monoamine oxidase B, a drug target enzyme monotopically inserted into the mitochondrial outer membrane

AU - Binda, Claudia

AU - Hubálek, Frantisek

AU - Li, Min

AU - Edmondson, Dale E.

AU - Mattevi, Andrea

PY - 2004/4/30

Y1 - 2004/4/30

N2 - Monoamine oxidase B (MAO B) is an outer mitochondrial membrane protein that oxidizes arylalkylamine neurotransmitters and has been a valuable drug target for many neurological disorders. The 1.7 Å resolution structure of human MAO B shows the enzyme is dimeric with a C-terminal transmembrane helix protruding from each monomer and anchoring the protein to the membrane. This helix departs perpendicularly from the base of the structure in a different way with respect to other monotopic membrane proteins. Several apolar loops exposed on the protein surface are located in proximity of the C-terminal helix, providing additional membrane-binding interactions. One of these loops (residues 99-112) also functions in opening and closing the MAO B active site cavity, which suggests that the membrane may have a role in controlling substrate binding.

AB - Monoamine oxidase B (MAO B) is an outer mitochondrial membrane protein that oxidizes arylalkylamine neurotransmitters and has been a valuable drug target for many neurological disorders. The 1.7 Å resolution structure of human MAO B shows the enzyme is dimeric with a C-terminal transmembrane helix protruding from each monomer and anchoring the protein to the membrane. This helix departs perpendicularly from the base of the structure in a different way with respect to other monotopic membrane proteins. Several apolar loops exposed on the protein surface are located in proximity of the C-terminal helix, providing additional membrane-binding interactions. One of these loops (residues 99-112) also functions in opening and closing the MAO B active site cavity, which suggests that the membrane may have a role in controlling substrate binding.

KW - Flavin

KW - Human monoamine oxidase B structure

KW - MAO, monoamine oxidase

KW - Mitochondrial membrane

KW - Monotopic

UR - http://www.scopus.com/inward/record.url?scp=1942436240&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=1942436240&partnerID=8YFLogxK

U2 - 10.1016/S0014-5793(04)00209-1

DO - 10.1016/S0014-5793(04)00209-1

M3 - Article

C2 - 15111100

AN - SCOPUS:1942436240

VL - 564

SP - 225

EP - 228

JO - FEBS Letters

JF - FEBS Letters

SN - 0014-5793

IS - 3

ER -