PMID- 10368296
OWN - NLM
STAT- MEDLINE
DCOM- 19990506
LR  - 20170804
IS  - 0969-2126 (Print)
IS  - 0969-2126 (Linking)
VI  - 7
IP  - 3
DP  - 1999 Mar 15
TI  - A 30-angstrom-long U-shaped catalytic tunnel in the crystal structure of
      polyamine oxidase.
PG  - 265-76
AB  - BACKGROUND: Polyamines are essential for cell growth and differentiation;
      compounds interfering with their metabolism are potential anticancer agents.
      Polyamine oxidase (PAO) plays a central role in polyamine homeostasis. The enzyme
      utilises an FAD cofactor to catalyse the oxidation of the secondary amino groups 
      of spermine and spermidine. RESULTS: The first crystal structure of a polyamine
      oxidase has been determined to a resolution of 1.9 Angstroms. PAO from Zea mays
      contains two domains, which define a remarkable 30 Angstrom long U-shaped
      catalytic tunnel at their interface. The structure of PAO in complex with the
      inhibitor MDL72527 reveals the residues forming the catalytic machinery and
      unusual enzyme-inhibitor CH.O H bonds. A ring of glutamate and aspartate residues
      surrounding one of the two tunnel openings contributes to the steering of the
      substrate towards the inside of the tunnel. CONCLUSIONS: PAO specifically
      oxidizes substrates that have both primary and secondary amino groups. The
      complex with MDL72527 shows that the primary amino groups are essential for the
      proper alignment of the substrate with respect to the flavin. Conservation of an 
      N-terminal sequence motif indicates that PAO is member of a novel family of
      flavoenzymes. Among these, monoamine oxidase displays significant sequence
      homology with PAO, suggesting a similar overall folding topology.
FAU - Binda, C
AU  - Binda C
AD  - Dipartimento di Genetica e Microbiologia, Universita di Pavia, Via Abbiategrasso 
      207, I-27100 Pavia, Italy.
FAU - Coda, A
AU  - Coda A
FAU - Angelini, R
AU  - Angelini R
FAU - Federico, R
AU  - Federico R
FAU - Ascenzi, P
AU  - Ascenzi P
FAU - Mattevi, A
AU  - Mattevi A
LA  - eng
PT  - Comparative Study
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Structure
JT  - Structure (London, England : 1993)
JID - 101087697
RN  - 0 (Enzyme Inhibitors)
RN  - 0 (Plant Proteins)
RN  - 0 (Polyamines)
RN  - 146-14-5 (Flavin-Adenine Dinucleotide)
RN  - 1YVR349GN4 (MDL 72527)
RN  - EC 1.4.3.4 (Monoamine Oxidase)
RN  - EC 1.5.- (Oxidoreductases Acting on CH-NH Group Donors)
RN  - EC 1.5.3.- (polyamine oxidase)
RN  - V10TVZ52E4 (Putrescine)
SB  - IM
MH  - Amino Acid Sequence
MH  - Binding Sites
MH  - Catalytic Domain
MH  - Crystallography, X-Ray
MH  - Enzyme Inhibitors/pharmacology
MH  - Flavin-Adenine Dinucleotide/metabolism
MH  - Glycosylation
MH  - Hydrogen Bonding
MH  - Models, Molecular
MH  - Molecular Sequence Data
MH  - Monoamine Oxidase/chemistry
MH  - Oxidoreductases Acting on CH-NH Group Donors/antagonists & inhibitors/*chemistry
MH  - Plant Proteins/antagonists & inhibitors/*chemistry
MH  - Polyamines/metabolism
MH  - *Protein Conformation
MH  - Protein Processing, Post-Translational
MH  - Putrescine/analogs & derivatives/pharmacology
MH  - Sequence Alignment
MH  - Sequence Homology, Amino Acid
MH  - Substrate Specificity
MH  - Zea mays/enzymology
EDAT- 1999/06/16 00:00
MHDA- 1999/06/16 00:01
CRDT- 1999/06/16 00:00
PHST- 1999/06/16 00:00 [pubmed]
PHST- 1999/06/16 00:01 [medline]
PHST- 1999/06/16 00:00 [entrez]
AID - S0969-2126(99)80037-9 [pii]
PST - ppublish
SO  - Structure. 1999 Mar 15;7(3):265-76.