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7odc
From Proteopedia
| 7odc, resolution 1.60Å () | |||||||||
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| Ligands: | |||||||||
| Activity: | Ornithine decarboxylase, with EC number 4.1.1.17 | ||||||||
| Domains: | Orn_DAP_Arg_deC, Orn_Arg_deC_N | ||||||||
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| Resources: | FirstGlance, OCA, PDBsum, RCSB | ||||||||
| Coordinates: | save as pdb, mmCIF, xml | ||||||||
CRYSTAL STRUCTURE ORNITHINE DECARBOXYLASE FROM MOUSE, TRUNCATED 37 RESIDUES FROM THE C-TERMINUS, TO 1.6 ANGSTROM RESOLUTION
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.
Structure of mammalian ornithine decarboxylase at 1.6 A resolution: stereochemical implications of PLP-dependent amino acid decarboxylases., Kern AD, Oliveira MA, Coffino P, Hackert ML, Structure. 1999 May;7(5):567-81. PMID:10378276
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
Although, 7odc is a 1 chain structure, the biological relevant molecule for 7odc can be assembled from the contents of the deposited coordinates by the application of crystallographic symmetry operations to give a dimer. It can be downloaded. A sequence alignment and structural comparison of mouse ornithine decarboxylase (mODC) to mouse Antizyme Inhibitor (AzI, 3btn) show high sequence identity (~50%) and structural similarity between mODC and AzI monomers (RMSD value is 1.6 Å). The of mODC (red and lime) to mouse AzI crystallographic dimer (mAzI, cyan and blueviolet) is shown. Superposition of the of mAzI and mODC showing the inter-subunit variable loops (AzI residues 355–362 and 387–401). AzI loops are in black, and ODC loops are in yellow.
The two AzI monomers (cyan, blueviolet) have only (< 3.5 Å apart), while there are more contacts (83) between the two monomers of (red, lime). Moreover, the surface area buried by the two mODC monomers is significantly larger than the one buried by the AzI monomers. These features explain a very weak crystallographic AzI dimer.
The zipper, formed by conserved hydrophobic residues in mODC, stabilizes its dimeric structure. These residues involve F397(B), Y323(B), Y331(A), Y331(B), Y323(A), and F397(A) (the names of the chains are in brackets). The residue Y331 in the is substituted by S329 in AzI and interferes with the formation of a similar zipper in AzI. Hence, in this hydrophobic zipper is absent. Many residues, participating in the ODC interdimer interface interactions, are conserved among the ODCs from variuos organisms, but in AzI these residues are not conserved. Furthermore, the AzI conserved residues do not participate in interdimer interactions. For example, mODC possesses (K169–D364 and D134–K294) stabilizing the ODC homodimer. In AzI, these 4 corresponding residues (, respectively) are also present, but are too far apart to form a salt bridge. The two AzI monomers are positioned farther apart, in comparison ot ODC monomers, preventing the formation of interdimer interactions.
About this Structure
7ODC is a 1 chain structure of sequence from Mus musculus. Full crystallographic information is available from OCA.
References
- Kern AD, Oliveira MA, Coffino P, Hackert ML. Structure of mammalian ornithine decarboxylase at 1.6 A resolution: stereochemical implications of PLP-dependent amino acid decarboxylases. Structure. 1999 May;7(5):567-81. PMID:10378276
- Albeck S, Dym O, Unger T, Snapir Z, Bercovich Z, Kahana C. Crystallographic and biochemical studies revealing the structural basis for antizyme inhibitor function. Protein Sci. 2008 May;17(5):793-802. Epub 2008 Mar 27. PMID:18369191 doi:10.1110/ps.073427208
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