PMID- 10623504
OWN - NLM
STAT- MEDLINE
DCOM- 20000119
LR  - 20141120
IS  - 0022-2836 (Print)
IS  - 0022-2836 (Linking)
VI  - 295
IP  - 1
DP  - 2000 Jan 7
TI  - Crystal structure of human ornithine decarboxylase at 2.1 A resolution:
      structural insights to antizyme binding.
PG  - 7-16
AB  - The polyamines spermidine and spermine are ubiquitous and required for cell
      growth and differentiation in eukaryotes. Ornithine decarboxylase (ODC, EC
      4.1.1.17) performs the first step in polyamine biosynthesis, the decarboxylation 
      of ornithine to putrescine. Elevated polyamine levels can lead to down-regulation
      of ODC activity by enhancing the translation of antizyme mRNA, resulting in
      subsequent binding of antizyme to ODC monomers which targets ODC for proteolysis 
      by the 26S proteasome. The crystal structure of ornithine decarboxylase from
      human liver has been determined to 2.1 A resolution by molecular replacement
      using truncated mouse ODC (Delta425-461) as the search model and refined to a
      crystallographic R-factor of 21.2% and an R-free value of 28.8%. The human ODC
      model includes several regions that are disordered in the mouse ODC crystal
      structure, including one of two C-terminal basal degradation elements that have
      been demonstrated to independently collaborate with antizyme binding to target
      ODC for degradation by the 26S proteasome. The crystal structure of human ODC
      suggests that the C terminus, which contains basal degradation elements necessary
      for antizyme-induced proteolysis, is not buried by the structural core of
      homodimeric ODC as previously proposed. Analysis of the solvent-accessible
      surface area, surface electrostatic potential, and the conservation of primary
      sequence between human ODC and Trypanosoma brucei ODC provides clues to the
      identity of potential protein-binding-determinants in the putative antizyme
      binding element in human ODC.
CI  - Copyright 2000 Academic Press.
FAU - Almrud, J J
AU  - Almrud JJ
AD  - Department of Chemistry, The University of Texas at Austin, Austin, TX, 78712,
      USA.
FAU - Oliveira, M A
AU  - Oliveira MA
FAU - Kern, A D
AU  - Kern AD
FAU - Grishin, N V
AU  - Grishin NV
FAU - Phillips, M A
AU  - Phillips MA
FAU - Hackert, M L
AU  - Hackert ML
LA  - eng
SI  - PDB/2TOD
GR  - GM30105/GM/NIGMS NIH HHS/United States
GR  - R01AI34432/AI/NIAID NIH HHS/United States
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - Netherlands
TA  - J Mol Biol
JT  - Journal of molecular biology
JID - 2985088R
RN  - 0 (Ornithine Decarboxylase Inhibitors)
RN  - 0 (Polyamines)
RN  - 0 (Proteins)
RN  - 0 (Solvents)
RN  - 0 (ornithine decarboxylase antizyme)
RN  - EC 4.1.1.17 (Ornithine Decarboxylase)
SB  - IM
MH  - Amino Acid Sequence
MH  - Animals
MH  - Binding Sites
MH  - Crystallography, X-Ray
MH  - Dimerization
MH  - Humans
MH  - Liver/enzymology
MH  - Mice
MH  - Models, Molecular
MH  - Molecular Sequence Data
MH  - Ornithine Decarboxylase/*chemistry/genetics/*metabolism
MH  - Ornithine Decarboxylase Inhibitors
MH  - Polyamines/metabolism
MH  - Protein Conformation
MH  - Proteins/metabolism
MH  - Sequence Alignment
MH  - Solvents
MH  - Static Electricity
MH  - Structure-Activity Relationship
MH  - Trypanosoma brucei brucei/enzymology
EDAT- 2000/01/07 00:00
MHDA- 2000/01/07 00:01
CRDT- 2000/01/07 00:00
PHST- 2000/01/07 00:00 [pubmed]
PHST- 2000/01/07 00:01 [medline]
PHST- 2000/01/07 00:00 [entrez]
AID - 10.1006/jmbi.1999.3331 [doi]
AID - S0022-2836(99)93331-4 [pii]
PST - ppublish
SO  - J Mol Biol. 2000 Jan 7;295(1):7-16. doi: 10.1006/jmbi.1999.3331.