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| | <StructureSection load='3svj' size='340' side='right'caption='[[3svj]], [[Resolution|resolution]] 1.55Å' scene=''> | | <StructureSection load='3svj' size='340' side='right'caption='[[3svj]], [[Resolution|resolution]] 1.55Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[3svj]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/"diplococcus_pneumoniae"_(klein_1884)_weichselbaum_1886 "diplococcus pneumoniae" (klein 1884) weichselbaum 1886]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3SVJ OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3SVJ FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[3svj]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Streptococcus_pneumoniae Streptococcus pneumoniae]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3SVJ OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3SVJ FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=4LI:(4R)-3-(4-[4-(2-CHLOROPHENYL)PIPERAZIN-1-YL]-6-{[2-METHYL-6-(METHYLCARBAMOYL)PHENYL]AMINO}-1,3,5-TRIAZIN-2-YL)-N-METHYL-1,3-THIAZOLIDINE-4-CARBOXAMIDE'>4LI</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=NI:NICKEL+(II)+ION'>NI</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</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]] 1.55Å</td></tr> |
| - | <tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=OCS:CYSTEINESULFONIC+ACID'>OCS</scene></td></tr>
| + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=4LI:(4R)-3-(4-[4-(2-CHLOROPHENYL)PIPERAZIN-1-YL]-6-{[2-METHYL-6-(METHYLCARBAMOYL)PHENYL]AMINO}-1,3,5-TRIAZIN-2-YL)-N-METHYL-1,3-THIAZOLIDINE-4-CARBOXAMIDE'>4LI</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=NI:NICKEL+(II)+ION'>NI</scene>, <scene name='pdbligand=OCS:CYSTEINESULFONIC+ACID'>OCS</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene></td></tr> |
| - | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat"><div style='overflow: auto; max-height: 3em;'>[[3str|3str]]</div></td></tr>
| + | |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">defB, def3 ([https://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=1313 "Diplococcus pneumoniae" (Klein 1884) Weichselbaum 1886])</td></tr>
| + | |
| - | <tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[https://en.wikipedia.org/wiki/Peptide_deformylase Peptide deformylase], with EC number [https://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'>[https://proteopedia.org/fgij/fg.htm?mol=3svj FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3svj OCA], [https://pdbe.org/3svj PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3svj RCSB], [https://www.ebi.ac.uk/pdbsum/3svj PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3svj ProSAT]</span></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=3svj FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3svj OCA], [https://pdbe.org/3svj PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3svj RCSB], [https://www.ebi.ac.uk/pdbsum/3svj PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3svj ProSAT]</span></td></tr> |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[https://www.uniprot.org/uniprot/Q939R9_STREE Q939R9_STREE]] Removes the formyl group from the N-terminal Met of newly synthesized proteins. Requires at least a dipeptide for an efficient rate of reaction. N-terminal L-methionine is a prerequisite for activity but the enzyme has broad specificity at other positions (By similarity).[HAMAP-Rule:MF_00163]
| + | [https://www.uniprot.org/uniprot/DEF_STRR6 DEF_STRR6] Removes the formyl group from the N-terminal Met of newly synthesized proteins. Requires at least a dipeptide for an efficient rate of reaction. N-terminal L-methionine is a prerequisite for activity but the enzyme has broad specificity at other positions (By similarity). |
| | <div style="background-color:#fffaf0;"> | | <div style="background-color:#fffaf0;"> |
| | == Publication Abstract from PubMed == | | == Publication Abstract from PubMed == |
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| | </StructureSection> | | </StructureSection> |
| | [[Category: Large Structures]] | | [[Category: Large Structures]] |
| - | [[Category: Peptide deformylase]] | + | [[Category: Streptococcus pneumoniae]] |
| - | [[Category: Campobasso, N]] | + | [[Category: Campobasso N]] |
| - | [[Category: Ward, P]] | + | [[Category: Ward P]] |
| - | [[Category: Alpha-beta]]
| + | |
| - | [[Category: Hydrolase-hydrolase inhibitor complex]]
| + | |
| - | [[Category: Metal binding protein]]
| + | |
| Structural highlights
3svj is a 1 chain structure with sequence from Streptococcus pneumoniae. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
| | Method: | X-ray diffraction, Resolution 1.55Å |
| Ligands: | , , , , |
| Resources: | FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT |
Function
DEF_STRR6 Removes the formyl group from the N-terminal Met of newly synthesized proteins. Requires at least a dipeptide for an efficient rate of reaction. N-terminal L-methionine is a prerequisite for activity but the enzyme has broad specificity at other positions (By similarity).
Publication Abstract from PubMed
The continual bacterial adaptation to antibiotics creates an ongoing medical need for the development of novel therapeutics. Polypeptide deformylase (PDF) is a highly conserved bacterial enzyme, which is essential for viability. It has previously been shown that PDF inhibitors represent a promising new area for the development of antimicrobial agents, and that many of the best PDF inhibitors demonstrate slow, time dependent binding. In order to gain a better understanding of the mechanistic origin of this time dependent inhibition, we examined in detail the kinetics of PDF catalysis and inhibition by several different PDF inhibitors. Varying pH and solvent isotope led to clear changes in time dependent inhibition parameters, as did inclusion of NaCl, which binds to the active site metal of PDF. Quantitative analysis of these results demonstrated that the observed time dependence arises from slow binding of the inhibitors to the active site metal. However, we also found several metal binding inhibitors that displayed rapid, non-time dependent onset of inhibition. By a combination of structural and chemical modification studies, we show that metal binding is only slow when the rest of the inhibitor makes optimal hydrogen bonds within the subsites of PDF. Both of these interactions between the inhibitor and enzyme were found to be necessary to observe time dependent inhibition, as elimination of either leads to its loss.
Understanding the Origins of Time Dependent Inhibition by Polypeptide Deformylase Inhibitors.,Totoritis R, Duraiswami C, Taylor AN, Kerrigan JJ, Campobasso N, Ward P, King BW, Murray-Thompson MF, Jones AD, Van Aller G, Aubart KM, Zalacain M, Thrall SH, Meek TD, Schwartz B Biochemistry. 2011 Jun 28. PMID:21711014[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Totoritis R, Duraiswami C, Taylor AN, Kerrigan JJ, Campobasso N, Ward P, King BW, Murray-Thompson MF, Jones AD, Van Aller G, Aubart KM, Zalacain M, Thrall SH, Meek TD, Schwartz B. Understanding the Origins of Time Dependent Inhibition by Polypeptide Deformylase Inhibitors. Biochemistry. 2011 Jun 28. PMID:21711014 doi:10.1021/bi200655g
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