3iiq

From Proteopedia

(Difference between revisions)

Current revision

Crystallographic analysis of bacterial signal peptidase in ternary complex with Arylomycin A2 and a beta-sultam inhibitor

Structural highlights

3iiq is a 4 chain structure with sequence from Escherichia coli K-12 and Streptomyces sp.. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:	X-ray diffraction, Resolution 2Å
Ligands:	, , , , , , ,
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

LEP_ECOLI

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

Bacterial type I signal peptidase (SPase I), an essential membrane-bound endopeptidase with a unique Ser/Lys dyad mechanism, is being investigated as a potential novel antibiotic target. We present here binding and inhibition assays along with crystallographic data that shows that the lipohexapeptide-based natural product arylomycin A2 and the morpholino-beta-sultam derivative (BAL0019193) inhibit SPase I by binding to non-overlapping subsites near the catalytic center. The 2.0 A resolution crystal structure of the soluble catalytic domain of Escherichia coli SPase I (SPase I Delta2-75) in ternary complex with arylomycin A2 and BAL0019193 reveals the position of BAL0019193 adjacent to arylomycin A2 within the SPase I binding site. BAL0019193 binds in a noncovalent manner in close proximity to SPase I residues Ser88, Ser90, Lys145, Asn277, Ala279, and Glu307, as well as atom O45 of arylomycin A2. The binding mode of arylomycin A2 in this 2.0 A resolution ternary complex is compared to that seen in the previous 2.5 A resolution arylomycin A2-SPase cocrystal structure. This work contributes to our understanding of SPase I inhibitor/substrate recognition and should prove helpful in the further development of novel antibiotics based on the inhibition of SPase I.

Crystallographic analysis of bacterial signal peptidase in ternary complex with arylomycin A2 and a beta-sultam inhibitor.,Luo C, Roussel P, Dreier J, Page MG, Paetzel M Biochemistry. 2009 Sep 29;48(38):8976-84. PMID:19655811^[1]

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

References

↑ Luo C, Roussel P, Dreier J, Page MG, Paetzel M. Crystallographic analysis of bacterial signal peptidase in ternary complex with arylomycin A2 and a beta-sultam inhibitor. Biochemistry. 2009 Sep 29;48(38):8976-84. PMID:19655811 doi:10.1021/bi9009538

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/3iiq"

Categories: Escherichia coli K-12 | Large Structures | Streptomyces sp | Paetzel M

@@ Line 1: / Line 1: @@
-[[Image:3iiq.png|left|200px]]
-<!--
+==Crystallographic analysis of bacterial signal peptidase in ternary complex with Arylomycin A2 and a beta-sultam inhibitor==
-The line below this paragraph, containing "STRUCTURE_3iiq", creates the "Structure Box" on the page.
+<StructureSection load='3iiq' size='340' side='right'caption='[[3iiq]], [[Resolution|resolution]] 2.00&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'>[[3iiq]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/Escherichia_coli_K-12 Escherichia coli K-12] and [https://en.wikipedia.org/wiki/Streptomyces_sp. Streptomyces sp.]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3IIQ OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3IIQ 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&#8491;</td></tr>
--->
+<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=5PG:(2S)-(4-HYDROXYPHENYL)(METHYLAMINO)ETHANOIC+ACID'>5PG</scene>, <scene name='pdbligand=CCN:ACETONITRILE'>CCN</scene>, <scene name='pdbligand=DAL:D-ALANINE'>DAL</scene>, <scene name='pdbligand=DSE:N-METHYL-D-SERINE'>DSE</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=JZA:4-[(1,1-DIOXIDO-1,2-THIAZETIDIN-2-YL)CARBONYL]MORPHOLINE'>JZA</scene>, <scene name='pdbligand=M12:10-METHYLUNDECANOIC+ACID'>M12</scene>, <scene name='pdbligand=TRT:FRAGMENT+OF+TRITON+X-100'>TRT</scene></td></tr>
-{{STRUCTURE_3iiq|  PDB=3iiq  |  SCENE=  }}
+<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=3iiq FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3iiq OCA], [https://pdbe.org/3iiq PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3iiq RCSB], [https://www.ebi.ac.uk/pdbsum/3iiq PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3iiq ProSAT]</span></td></tr>
+</table>
+== Function ==
+[https://www.uniprot.org/uniprot/LEP_ECOLI LEP_ECOLI]
+== Evolutionary Conservation ==
+[[Image:Consurf_key_small.gif|200px|right]]
+Check<jmol>
+  <jmolCheckbox>
+    <scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/ii/3iiq_consurf.spt"</scriptWhenChecked>
+    <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked>
+    <text>to colour the structure by Evolutionary Conservation</text>
+  </jmolCheckbox>
+</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=3iiq ConSurf].
+<div style="clear:both"></div>
+<div style="background-color:#fffaf0;">
+== Publication Abstract from PubMed ==
+Bacterial type I signal peptidase (SPase I), an essential membrane-bound endopeptidase with a unique Ser/Lys dyad mechanism, is being investigated as a potential novel antibiotic target. We present here binding and inhibition assays along with crystallographic data that shows that the lipohexapeptide-based natural product arylomycin A2 and the morpholino-beta-sultam derivative (BAL0019193) inhibit SPase I by binding to non-overlapping subsites near the catalytic center. The 2.0 A resolution crystal structure of the soluble catalytic domain of Escherichia coli SPase I (SPase I Delta2-75) in ternary complex with arylomycin A2 and BAL0019193 reveals the position of BAL0019193 adjacent to arylomycin A2 within the SPase I binding site. BAL0019193 binds in a noncovalent manner in close proximity to SPase I residues Ser88, Ser90, Lys145, Asn277, Ala279, and Glu307, as well as atom O45 of arylomycin A2. The binding mode of arylomycin A2 in this 2.0 A resolution ternary complex is compared to that seen in the previous 2.5 A resolution arylomycin A2-SPase cocrystal structure. This work contributes to our understanding of SPase I inhibitor/substrate recognition and should prove helpful in the further development of novel antibiotics based on the inhibition of SPase I.
-===Crystallographic analysis of bacterial signal peptidase in ternary complex with Arylomycin A2 and a beta-sultam inhibitor===
+Crystallographic analysis of bacterial signal peptidase in ternary complex with arylomycin A2 and a beta-sultam inhibitor.,Luo C, Roussel P, Dreier J, Page MG, Paetzel M Biochemistry. 2009 Sep 29;48(38):8976-84. PMID:19655811<ref>PMID:19655811</ref>
+From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
-<!--
+</div>
-The line below this paragraph, {{ABSTRACT_PUBMED_19655811}}, adds the Publication Abstract to the page
+<div class="pdbe-citations 3iiq" style="background-color:#fffaf0;"></div>
-(as it appears on PubMed at http://www.pubmed.gov), where 19655811 is the PubMed ID number.
+== References ==
--->
+<references/>
-{{ABSTRACT_PUBMED_19655811}}
+__TOC__
+</StructureSection>
-==About this Structure==
+[[Category: Escherichia coli K-12]]
-[[3iiq]] is a 4 chain structure with sequence from [http://en.wikipedia.org/wiki/Escherichia_coli Escherichia coli] and [http://en.wikipedia.org/wiki/Streptomyces_sp. Streptomyces sp.]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3IIQ OCA].
+[[Category: Large Structures]]
+[[Category: Streptomyces sp]]
-==Reference==
+[[Category: Paetzel M]]
-<ref group="xtra">PMID:019655811</ref><references group="xtra"/>
-[[Category: Escherichia coli]]
-[[Category: Signal peptidase I]]
-[[Category: Streptomyces sp.]]
-[[Category: Paetzel, M.]]
-[[Category: Antibiotic]]
-[[Category: Biaryl bridge]]
-[[Category: Hydrolase-antibiotic-inhibitor complex]]
-[[Category: Lipopeptide]]
-[[Category: Morpholino beta-sultam]]
-[[Category: Peptidase]]
-[[Category: Ser/lys dyad]]
-[[Category: Serine protease]]

3iiq

From Proteopedia

Current revision

Crystallographic analysis of bacterial signal peptidase in ternary complex with Arylomycin A2 and a beta-sultam inhibitor

Structural highlights

Function

Evolutionary Conservation

Publication Abstract from PubMed

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

Views

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