1g2a

<StructureSection load='1g2a' size='340' side='right' caption='[[1g2a]], [[Resolution|resolution]] 1.75&Aring;' scene=''>

<table><tr><td colspan='2'>[[1g2a]] is a 3 chain structure with sequence from [http://en.wikipedia.org/wiki/"bacillus_coli"_migula_1895 "bacillus coli" migula 1895]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1G2A OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1G2A FirstGlance]. <br>

</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=BB2:ACTINONIN'>BB2</scene>, <scene name='pdbligand=NI:NICKEL+(II)+ION'>NI</scene></td></tr>

<tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[1g27|1g27]]</td></tr>

<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">DEF ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=562 "Bacillus coli" Migula 1895])</td></tr>

<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Formylmethionine_deformylase Formylmethionine deformylase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.5.1.31 3.5.1.31] </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=1g2a FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1g2a OCA], [http://pdbe.org/1g2a PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=1g2a RCSB], [http://www.ebi.ac.uk/pdbsum/1g2a PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=1g2a ProSAT]</span></td></tr>

[[http://www.uniprot.org/uniprot/DEF_ECOLI DEF_ECOLI]] 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.[HAMAP-Rule:MF_00163]

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== Publication Abstract from PubMed ==

Peptide deformylase (PDF) is an essential bacterial metalloenzyme which deformylates the N-formylmethionine of newly synthesized polypeptides and as such represents a novel target for antibacterial chemotherapy. To identify novel PDF inhibitors, we screened a metalloenzyme inhibitor library and identified an N-formyl-hydroxylamine derivative, BB-3497, and a related natural hydroxamic acid antibiotic, actinonin, as potent and selective inhibitors of PDF. To elucidate the interactions that contribute to the binding affinity of these inhibitors, we determined the crystal structures of BB-3497 and actinonin bound to Escherichia coli PDF at resolutions of 2.1 and 1.75 A, respectively. In both complexes, the active-site metal atom was pentacoordinated by the side chains of Cys 90, His 132, and His 136 and the two oxygen atoms of N-formyl-hydroxylamine or hydroxamate. BB-3497 had activity against gram-positive bacteria, including methicillin-resistant Staphylococcus aureus and vancomycin-resistant Enterococcus faecalis, and activity against some gram-negative bacteria. Time-kill analysis showed that the mode of action of BB-3497 was primarily bacteriostatic. The mechanism of resistance was via mutations within the formyltransferase gene, as previously described for actinonin. While actinonin and its derivatives have not been used clinically because of their poor pharmacokinetic properties, BB-3497 was shown to be orally bioavailable. A single oral dose of BB-3497 given 1 h after intraperitoneal injection of S. aureus Smith or methicillin-resistant S. aureus protected mice from infection with median effective doses of 8 and 14 mg/kg of body weight, respectively. These data validate PDF as a novel target for the design of a new generation of antibacterial agents.

Antibiotic activity and characterization of BB-3497, a novel peptide deformylase inhibitor.,Clements JM, Beckett RP, Brown A, Catlin G, Lobell M, Palan S, Thomas W, Whittaker M, Wood S, Salama S, Baker PJ, Rodgers HF, Barynin V, Rice DW, Hunter MG Antimicrob Agents Chemother. 2001 Feb;45(2):563-70. PMID:11158755<ref>PMID:11158755</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>

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<div class="pdbe-citations 1g2a" style="background-color:#fffaf0;"></div>

== References ==

<references/>

[[Category: Bacillus coli migula 1895]]

[[Category: Formylmethionine deformylase]]

[[Category: Baker, P J]]

[[Category: Barynin, V]]

[[Category: Beckett, P]]

[[Category: Brown, A]]

[[Category: Catlin, C]]

[[Category: Clements, J M]]

[[Category: Hunter, M G]]

[[Category: Lobell, M]]

[[Category: Palan, S]]

[[Category: Rice, D W]]

[[Category: Rodgers, H F]]

[[Category: Thomas, W]]

[[Category: Whittaker, M]]

[[Category: Polypeptide deformylase]]