PMID- 10378276
OWN - NLM
STAT- MEDLINE
DCOM- 19990806
LR  - 20190915
IS  - 0969-2126 (Print)
IS  - 0969-2126 (Linking)
VI  - 7
IP  - 5
DP  - 1999 May
TI  - Structure of mammalian ornithine decarboxylase at 1.6 A resolution:
      stereochemical implications of PLP-dependent amino acid decarboxylases.
PG  - 567-81
AB  - BACKGROUND: Pyridoxal-5'-phosphate (PLP) dependent enzymes catalyze a broad range
      of reactions, resulting in bond cleavage at C alpha, C beta, or C gamma carbons
      of D and L amino acid substrates. Ornithine decarboxylase (ODC) is a
      PLP-dependent enzyme that controls a critical step in the biosynthesis of
      polyamines, small organic polycations whose controlled levels are essential for
      proper growth. ODC inhibition has applications for the treatment of certain
      cancers and parasitic ailments such as African sleeping sickness. RESULTS: The
      structure of truncated mouse ODC (mODC') was determined by multiple isomorphous
      replacement methods and refined to 1.6 A resolution. This is the first structure 
      of a Group IV decarboxylase. The monomer contains two domains: an alpha/beta
      barrel that binds the cofactor, and a second domain consisting mostly of beta
      structure. Only the dimer is catalytically active, as the active sites are
      constructed of residues from both monomers. The interactions stabilizing the
      dimer shed light on its regulation by antizyme. The overall structure and the
      environment of the cofactor are compared with those of alanine racemase.
      CONCLUSIONS: The analysis of the mODC' structure and its comparison with alanine 
      racemase, together with modeling studies of the external aldimine intermediate,
      provide insight into the stereochemical characteristics of PLP-dependent
      decarboxylation. The structure comparison reveals stereochemical differences with
      other PLP-dependent enzymes and the bacterial ODC. These characteristics may be
      exploited in the design of new inhibitors specific for eukaryotic and bacterial
      ODCs, and provide the basis for a detailed understanding of the mechanism by
      which these enzymes regulate reaction specificity.
FAU - Kern, A D
AU  - Kern AD
AD  - Department of Chemistry and Biochemistry, University of Texas at Austin 78712,
      USA.
FAU - Oliveira, M A
AU  - Oliveira MA
FAU - Coffino, P
AU  - Coffino P
FAU - Hackert, M L
AU  - Hackert ML
LA  - eng
SI  - PDB/7ODC
GR  - GM30105/GM/NIGMS NIH HHS/United States
GR  - GM45335/GM/NIGMS NIH HHS/United States
GR  - RR-01646/RR/NCRR NIH HHS/United States
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, Non-P.H.S.
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - United States
TA  - Structure
JT  - Structure (London, England : 1993)
JID - 101087697
RN  - 5V5IOJ8338 (Pyridoxal Phosphate)
RN  - EC 4.1.1.17 (Ornithine Decarboxylase)
SB  - IM
MH  - Amino Acid Sequence
MH  - Animals
MH  - Binding Sites
MH  - Dimerization
MH  - Enzyme Stability
MH  - Mice
MH  - Models, Molecular
MH  - Molecular Sequence Data
MH  - Ornithine Decarboxylase/*chemistry/metabolism
MH  - Protein Conformation
MH  - Protein Folding
MH  - Pyridoxal Phosphate/*metabolism
MH  - Sequence Homology, Amino Acid
MH  - Stereoisomerism
EDAT- 1999/06/23 00:00
MHDA- 1999/06/23 00:01
CRDT- 1999/06/23 00:00
PHST- 1999/06/23 00:00 [pubmed]
PHST- 1999/06/23 00:01 [medline]
PHST- 1999/06/23 00:00 [entrez]
AID - S0969-2126(99)80073-2 [pii]
AID - 10.1016/s0969-2126(99)80073-2 [doi]
PST - ppublish
SO  - Structure. 1999 May;7(5):567-81. doi: 10.1016/s0969-2126(99)80073-2.