1zy1
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X-ray structure of peptide deformylase from Arabidopsis thaliana (AtPDF1A) in complex with Met-Ala-Ser
OverviewOverview
Peptide deformylase (PDF) inhibitors have a strong potential to be used as, a new class of antibiotics. However, recent studies have shown that the, mitochondria of most eukaryotes, including humans, contain an essential, PDF, PDF1A. The crystal structure of the Arabidopsis thaliana PDF1A, (AtPDF1A), considered representative of PDF1As in general, has been, determined. This structure displays several similarities to that of known, bacterial PDFs. AtPDF1A behaves as a dimer, with the C-terminal residues, responsible for linking the two subunits. This arrangement is similar to, that of Leptospira interrogans PDF, the only other dimeric PDF identified, to date. AtPDF1A is the first PDF for which zinc has been identified as, the catalytic ion. However, the zinc binding pocket does not differ from, the binding pockets of PDFs with iron rather than zinc. The crystal, structure of AtPDF1A in complex with a substrate analog revealed that the, substrate binding pocket of PDF1A displays strong modifications. The S1', binding pocket is significantly narrower, due to the creation of a floor, from residues present in all PDF1As but not in bacterial PDFs. A true S3', pocket is created by the residues of a helical CD-loop, which is very long, in PDF1As. Finally, these modified substrate binding pockets modify the, position of the substrate in the active site. These differences provide, guidelines for the design of bacterial PDF inhibitors that will not target, mitochondrial PDFs.
About this StructureAbout this Structure
1ZY1 is a Single protein structure of sequence from Arabidopsis thaliana with ZN as ligand. Active as Peptide deformylase, with EC number 3.5.1.88 Full crystallographic information is available from OCA.
ReferenceReference
The crystal structure of mitochondrial (Type 1A) peptide deformylase provides clear guidelines for the design of inhibitors specific for the bacterial forms., Fieulaine S, Juillan-Binard C, Serero A, Dardel F, Giglione C, Meinnel T, Ferrer JL, J Biol Chem. 2005 Dec 23;280(51):42315-24. Epub 2005 Sep 28. PMID:16192279
Page seeded by OCA on Wed Nov 21 07:43:46 2007