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1g27

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Revision as of 06:51, 19 June 2019

CRYSTAL STRUCTURE OF E.COLI POLYPEPTIDE DEFORMYLASE COMPLEXED WITH THE INHIBITOR BB-3497

Structural highlights

1g27 is a 3 chain structure with sequence from "bacillus_coli"_migula_1895 "bacillus coli" migula 1895. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Ligands:	,
Related:	1g2a
Gene:	DEF ("Bacillus coli" Migula 1895)
Activity:	Formylmethionine deformylase, with EC number 3.5.1.31
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

[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]

Evolutionary Conservation

Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.

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^[1]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

References

↑ 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. Antibiotic activity and characterization of BB-3497, a novel peptide deformylase inhibitor. Antimicrob Agents Chemother. 2001 Feb;45(2):563-70. PMID:11158755 doi:10.1128/AAC.45.2.563-570.2001

1 Structural highlights
2 Function
3 Evolutionary Conservation
4 Publication Abstract from PubMed
5 References

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/1g27"

@@ Line 1: / Line 1: @@
 ==CRYSTAL STRUCTURE OF E.COLI POLYPEPTIDE DEFORMYLASE COMPLEXED WITH THE INHIBITOR BB-3497==
-<StructureSection load='1g27' size='340' side='right' caption='[[1g27]], [[Resolution|resolution]] 2.10&Aring;' scene=''>
+<StructureSection load='1g27' size='340' side='right'caption='[[1g27]], [[Resolution|resolution]] 2.10&Aring;' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[1g27]] is a 3 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1G27 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1G27 FirstGlance]. <br>
+<table><tr><td colspan='2'>[[1g27]] 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=1G27 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1G27 FirstGlance]. <br>
 </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=BB1:2-[(FORMYL-HYDROXY-AMINO)-METHYL]-HEXANOIC+ACID+(1-DIMETHYLCARBAMOYL-2,2-DIMETHYL-PROPYL)-AMIDE'>BB1</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">[[1g2a|1g2a]]</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=1g27 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1g27 OCA], [http://pdbe.org/1g27 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=1g27 RCSB], [http://www.ebi.ac.uk/pdbsum/1g27 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=1g27 ProSAT]</span></td></tr>
@@ Line 15: / Line 16: @@
 Check<jmol>
   <jmolCheckbox>
-    <scriptWhenChecked>select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/g2/1g27_consurf.spt"</scriptWhenChecked>
+    <scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/g2/1g27_consurf.spt"</scriptWhenChecked>
     <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked>
     <text>to colour the structure by Evolutionary Conservation</text>
@@ Line 34: / Line 35: @@
 __TOC__
 </StructureSection>
+[[Category: Bacillus coli migula 1895]]
 [[Category: Formylmethionine deformylase]]
+[[Category: Large Structures]]
 [[Category: Baker, P J]]
 [[Category: Barynin, V]]

1g27

From Proteopedia

Revision as of 06:51, 19 June 2019

CRYSTAL STRUCTURE OF E.COLI POLYPEPTIDE DEFORMYLASE COMPLEXED WITH THE INHIBITOR BB-3497

Structural highlights

Function

Evolutionary Conservation

Publication Abstract from PubMed

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

Views

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