PDBsum entry 7odc

Lyase

PDB id: 7odc

Contents

Protein chain

387 a.a. *

Ligands

PLP

Waters ×421

* Residue conservation analysis

PDB id:

7odc

Name:

Lyase

Title:

Crystal structure ornithine decarboxylase from mouse, truncated 37 residues from thE C-terminus, to 1.6 angstrom resolution

Structure:

Protein (ornithine decarboxylase). Chain: a. Synonym: odc, modc, modc'. Engineered: yes. Mutation: yes. Other_details: schiff-base linkage between plp and k69

Source:

Mus musculus. House mouse. Organism_taxid: 10090. Cell_line: s49.1. Tissue: lymphoma. Expressed in: escherichia coli. Expression_system_taxid: 562. Other_details: the gene was cloned from a balb-c mouse lymphoma cell line in which the odc gene was amplified by selection with dfmo. The

Biol. unit:

Dimer (from PDB file)

Resolution:

1.60Å R-factor: 0.199 R-free: 0.232

Authors:

A.D.Kern,M.A.Oliveira,P.Coffino,M.L.Hackert

Key ref:

A.D.Kern et al. (1999). Structure of mammalian ornithine decarboxylase at 1.6 A resolution: stereochemical implications of PLP-dependent amino acid decarboxylases. Structure, 7, 567-581. PubMed id: 10378276 DOI: 10.1016/S0969-2126(99)80073-2

Date:

03-Mar-99 Release date: 22-Oct-99

Protein chain

P00860  (DCOR_MOUSE) -  Ornithine decarboxylase from Mus musculus

Seq: 461 a.a.

Struc: 387 a.a.*

* PDB and UniProt seqs differ at 1 residue position (black cross)

Enzyme reactions

• Enzyme class: E.C.4.1.1.17 - ornithine decarboxylase.
• Pathway: Spermine Biosynthesis
• Reaction: L-ornithine + H⁺ = putrescine + CO2
• Cofactor: Pyridoxal 5'-phosphate

Pyridoxal 5'-phosphate (Bound ligand (Het Group name = PLP) matches with 93.75% similarity)

Molecule diagrams generated from .mol files obtained from the KEGG ftp site

reference

DOI no: 10.1016/S0969-2126(99)80073-2

Structure 7:567-581 (1999)

PubMed id: 10378276

Structure of mammalian ornithine decarboxylase at 1.6 A resolution: stereochemical implications of PLP-dependent amino acid decarboxylases.

A.D.Kern, M.A.Oliveira, P.Coffino, M.L.Hackert.

ABSTRACT

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.

Selected figure(s)

Figure 5.
Figure 5. Active site of mODC′ and comparison with ALR. (a) Schematic drawing of the mODC′ active site illustrating the hydrogen-bond interactions. Residues shown in bold face are nearer the viewer. (b) Stereo figure of the active site of mODC′ with electron density superimposed with its model. K69 of mODC′ is in Schiff-base linkage to the cofactor, E274 pairs with the pyridine ring nitrogen N1, and H197 stacks on the si face of the cofactor ring. Note the angle between K69 and the pyridine ring of the cofactor exposing the si face. The map is a 2F[o]–F[c] map at 1.6 Å resolution contoured at 1.2σ. (c) A view of the ALR and mODC′ active sites resulting from the superposition of their cofactor rings. The mODC′ active site is depicted in light gray. The figures were generated using BOBSCRIPT [83], MOLSCRIPT [80] and Raster3D [81].

The above figure is reprinted by permission from Cell Press: Structure (1999, 7, 567-581) copyright 1999.

Figure was selected by an automated process.