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| | ==Crystal structure of a human-like mitochondrial peptide deformylase in complex with Met-Ala-Ser== | | ==Crystal structure of a human-like mitochondrial peptide deformylase in complex with Met-Ala-Ser== |
| - | <StructureSection load='4je8' size='340' side='right' caption='[[4je8]], [[Resolution|resolution]] 2.40Å' scene=''> | + | <StructureSection load='4je8' size='340' side='right'caption='[[4je8]], [[Resolution|resolution]] 2.40Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[4je8]] is a 4 chain structure with sequence from [http://en.wikipedia.org/wiki/Arath Arath]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4JE8 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4JE8 FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[4je8]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/Arabidopsis_thaliana Arabidopsis thaliana]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4JE8 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4JE8 FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></td></tr> | + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.4Å</td></tr> |
| - | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[4je6|4je6]], [[4je7|4je7]]</td></tr>
| + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></td></tr> |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">At1g15390, def, DEF1, F9L1.34, F9L1_34, PDF1A ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=3702 ARATH])</td></tr> | + | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=4je8 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4je8 OCA], [https://pdbe.org/4je8 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4je8 RCSB], [https://www.ebi.ac.uk/pdbsum/4je8 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4je8 ProSAT]</span></td></tr> |
| - | <tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Peptide_deformylase Peptide deformylase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.5.1.88 3.5.1.88] </span></td></tr>
| + | |
| - | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4je8 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4je8 OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4je8 RCSB], [http://www.ebi.ac.uk/pdbsum/4je8 PDBsum]</span></td></tr> | + | |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/DEF1A_ARATH DEF1A_ARATH]] Removes the formyl group from the N-terminal Met of newly synthesized proteins.<ref>PMID:11060042</ref> | + | [https://www.uniprot.org/uniprot/DEF1A_ARATH DEF1A_ARATH] Removes the formyl group from the N-terminal Met of newly synthesized proteins.<ref>PMID:11060042</ref> |
| | <div style="background-color:#fffaf0;"> | | <div style="background-color:#fffaf0;"> |
| | == Publication Abstract from PubMed == | | == Publication Abstract from PubMed == |
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| | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> |
| | </div> | | </div> |
| | + | <div class="pdbe-citations 4je8" style="background-color:#fffaf0;"></div> |
| | == References == | | == References == |
| | <references/> | | <references/> |
| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Arath]] | + | [[Category: Arabidopsis thaliana]] |
| - | [[Category: Peptide deformylase]] | + | [[Category: Large Structures]] |
| - | [[Category: Fieulaine, S]] | + | [[Category: Fieulaine S]] |
| - | [[Category: Giglione, C]] | + | [[Category: Giglione C]] |
| - | [[Category: Meinnel, T]] | + | [[Category: Meinnel T]] |
| - | [[Category: Hydrolase-peptide complex]]
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| - | [[Category: Mitochondrial]]
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| Structural highlights
Function
DEF1A_ARATH Removes the formyl group from the N-terminal Met of newly synthesized proteins.[1]
Publication Abstract from PubMed
Peptide deformylases (PDFs), which are essential and ubiquitous enzymes involved in the removal of the N-formyl group from nascent chains, are classified into four subtypes based on the structural and sequence similarity of specific conserved domains. All PDFs share a similar three-dimensional structure, are functionally interchangeable in vivo and display similar properties in vitro, indicating that their molecular mechanism has been conserved during evolution. The human mitochondrial PDF is the only exception as despite its conserved fold it reveals a unique substrate-binding pocket together with an unusual kinetic behaviour. Unlike human PDF, the closely related mitochondrial PDF1As from plants have catalytic efficiencies and enzymatic parameters that are similar to those of other classes of PDFs. Here, the aim was to identify the structural basis underlying the properties of human PDF compared with all other PDFs by focusing on plant mitochondrial PDF1A. The construction of a chimaera composed of plant PDF1A with the nonrandom substitutions found in a conserved motif of its human homologue converted it into an enzyme with properties similar to the human enzyme, indicating the crucial role of these positions. The crystal structure of this human-like plant PDF revealed that substitution of two residues leads to a reduction in the volume of the ligand-binding site together with the introduction of negative charges, unravelling the origin of the weak affinity of human PDF for its substrate. In addition, the substitution of the two residues of human PDF modifies the transition state of the reaction through alteration of the network of interactions between the catalytic residues and the substrate, leading to an overall reduced reaction rate.
Understanding the highly efficient catalysis of prokaryotic peptide deformylases by shedding light on the determinants specifying the low activity of the human counterpart.,Fieulaine S, Desmadril M, Meinnel T, Giglione C Acta Crystallogr D Biol Crystallogr. 2014 Feb;70(Pt 2):242-52. doi:, 10.1107/S1399004713026461. Epub 2014 Jan 17. PMID:24531459[2]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Giglione C, Serero A, Pierre M, Boisson B, Meinnel T. Identification of eukaryotic peptide deformylases reveals universality of N-terminal protein processing mechanisms. EMBO J. 2000 Nov 1;19(21):5916-29. PMID:11060042 doi:10.1093/emboj/19.21.5916
- ↑ Fieulaine S, Desmadril M, Meinnel T, Giglione C. Understanding the highly efficient catalysis of prokaryotic peptide deformylases by shedding light on the determinants specifying the low activity of the human counterpart. Acta Crystallogr D Biol Crystallogr. 2014 Feb;70(Pt 2):242-52. doi:, 10.1107/S1399004713026461. Epub 2014 Jan 17. PMID:24531459 doi:http://dx.doi.org/10.1107/S1399004713026461
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