1g27: Difference between revisions

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[[Image:1g27.gif|left|200px]]


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==CRYSTAL STRUCTURE OF E.COLI POLYPEPTIDE DEFORMYLASE COMPLEXED WITH THE INHIBITOR BB-3497==
The line below this paragraph, containing "STRUCTURE_1g27", creates the "Structure Box" on the page.
<StructureSection load='1g27' size='340' side='right'caption='[[1g27]], [[Resolution|resolution]] 2.10&Aring;' scene=''>
You may change the PDB parameter (which sets the PDB file loaded into the applet)
== Structural highlights ==
or the SCENE parameter (which sets the initial scene displayed when the page is loaded),
<table><tr><td colspan='2'>[[1g27]] is a 3 chain structure with sequence from [https://en.wikipedia.org/wiki/Escherichia_coli Escherichia coli]. 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 [https://proteopedia.org/fgij/fg.htm?mol=1G27 FirstGlance]. <br>
or leave the SCENE parameter empty for the default display.
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.1&#8491;</td></tr>
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<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><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>
{{STRUCTURE_1g27|  PDB=1g27  |  SCENE= }}
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=1g27 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1g27 OCA], [https://pdbe.org/1g27 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1g27 RCSB], [https://www.ebi.ac.uk/pdbsum/1g27 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1g27 ProSAT]</span></td></tr>
 
</table>
'''CRYSTAL STRUCTURE OF E.COLI POLYPEPTIDE DEFORMYLASE COMPLEXED WITH THE INHIBITOR BB-3497'''
== Function ==
 
[https://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]
 
== Evolutionary Conservation ==
==Overview==
[[Image:Consurf_key_small.gif|200px|right]]
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.
Check<jmol>
 
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==About this Structure==
    <scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/g2/1g27_consurf.spt"</scriptWhenChecked>
1G27 is a [[Single protein]] structure of sequence from [http://en.wikipedia.org/wiki/Escherichia_coli Escherichia coli]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1G27 OCA].  
    <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked>
 
    <text>to colour the structure by Evolutionary Conservation</text>
==Reference==
  </jmolCheckbox>
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:[http://www.ncbi.nlm.nih.gov/pubmed/11158755 11158755]
</jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/main_output.php?pdb_ID=1g27 ConSurf].
<div style="clear:both"></div>
__TOC__
</StructureSection>
[[Category: Escherichia coli]]
[[Category: Escherichia coli]]
[[Category: Formylmethionine deformylase]]
[[Category: Large Structures]]
[[Category: Single protein]]
[[Category: Baker PJ]]
[[Category: Baker, P J.]]
[[Category: Barynin V]]
[[Category: Barynin, V.]]
[[Category: Beckett P]]
[[Category: Beckett, P.]]
[[Category: Brown A]]
[[Category: Brown, A.]]
[[Category: Catlin C]]
[[Category: Catlin, C.]]
[[Category: Clements JM]]
[[Category: Clements, J M.]]
[[Category: Hunter MG]]
[[Category: Hunter, M G.]]
[[Category: Lobell M]]
[[Category: Lobell, M.]]
[[Category: Palan S]]
[[Category: Palan, S.]]
[[Category: Rice DW]]
[[Category: Rice, D W.]]
[[Category: Rodgers HF]]
[[Category: Rodgers, H F.]]
[[Category: Thomas W]]
[[Category: Thomas, W.]]
[[Category: Whittaker M]]
[[Category: Whittaker, M.]]
[[Category: Bb-3497]]
[[Category: Inhibition]]
[[Category: Polypeptide deformylase]]
''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Fri May  2 17:02:37 2008''

Latest revision as of 10:21, 7 February 2024

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

Structural highlights

1g27 is a 3 chain structure with sequence from Escherichia coli. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:X-ray diffraction, Resolution 2.1Å
Ligands:,
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.

1g27, resolution 2.10Å

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OCA
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