1hb4

From Proteopedia

(Difference between revisions)
Jump to: navigation, search
Current revision (12:23, 13 December 2023) (edit) (undo)
 
(8 intermediate revisions not shown.)
Line 1: Line 1:
-
{{STRUCTURE_1hb4| PDB=1hb4 | SCENE= }}
 
-
===ISOPENICILLIN N SYNTHASE FROM ASPERGILLUS NIDULANS (OXYGEN EXPOSED PRODUCT FROM ANAEROBIC ACOV FE COMPLEX)===
 
-
{{ABSTRACT_PUBMED_11755401}}
 
-
==About this Structure==
+
==ISOPENICILLIN N SYNTHASE FROM ASPERGILLUS NIDULANS (OXYGEN EXPOSED PRODUCT FROM ANAEROBIC ACOV FE COMPLEX)==
-
[[1hb4]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Emericella_nidulans Emericella nidulans]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1HB4 OCA].
+
<StructureSection load='1hb4' size='340' side='right'caption='[[1hb4]], [[Resolution|resolution]] 1.50&Aring;' scene=''>
 +
== Structural highlights ==
 +
<table><tr><td colspan='2'>[[1hb4]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Aspergillus_nidulans Aspergillus nidulans]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1HB4 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1HB4 FirstGlance]. <br>
 +
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.5&#8491;</td></tr>
 +
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=FE2:FE+(II)+ION'>FE2</scene>, <scene name='pdbligand=SCV:N6-[(1S)-2-{[(1R)-1-CARBOXY-2-METHYLPROPYL]OXY}-1-(MERCAPTOCARBONYL)-2-OXOETHYL]-6-OXO-L-LYSINE'>SCV</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene></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=1hb4 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1hb4 OCA], [https://pdbe.org/1hb4 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1hb4 RCSB], [https://www.ebi.ac.uk/pdbsum/1hb4 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1hb4 ProSAT]</span></td></tr>
 +
</table>
 +
== Function ==
 +
[https://www.uniprot.org/uniprot/IPNA_EMENI IPNA_EMENI] Isopenicillin N synthase; part of the gene cluster that mediates the biosynthesis of penicillin, the world's most important antibiotic (PubMed:3319778, PubMed:11755401). IpnA catalyzes the cyclization of the tripeptide N-[(5S)-5-amino-5-carboxypentanoyl]-L-cysteinyl-D-valine (LLD-ACV or ACV) to form isopenicillin N (IPN) that contains the beta-lactam nucleus (PubMed:3319778, PubMed:11755401, PubMed:28703303). The penicillin biosynthesis occurs via 3 enzymatic steps, the first corresponding to the production of the tripeptide N-[(5S)-5-amino-5-carboxypentanoyl]-L-cysteinyl-D-valine (LLD-ACV or ACV) by the NRPS acvA. The tripeptide ACV is then cyclized to isopenicillin N (IPN) by the isopenicillin N synthase ipnA that forms the beta-lactam nucleus. Finally, the alpha-aminoadipyl side chain is exchanged for phenylacetic acid by the isopenicillin N acyltransferase penDE to yield penicillin in the peroxisomal matrix (By similarity).[UniProtKB:P08703]<ref>PMID:11755401</ref> <ref>PMID:28703303</ref> <ref>PMID:3319778</ref>
 +
== 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/hb/1hb4_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=1hb4 ConSurf].
 +
<div style="clear:both"></div>
 +
<div style="background-color:#fffaf0;">
 +
== Publication Abstract from PubMed ==
 +
BACKGROUND: Isopenicillin N synthase (IPNS) catalyses formation of bicyclic isopenicillin N, precursor to all penicillin and cephalosporin antibiotics, from the linear tripeptide delta-(L-alpha-aminoadipoyl)-L-cysteinyl-D-valine. IPNS is a non-haem iron(II)-dependent enzyme which utilises the full oxidising potential of molecular oxygen in catalysing the bicyclisation reaction. The reaction mechanism is believed to involve initial formation of the beta-lactam ring (via a thioaldehyde intermediate) to give an iron(IV)-oxo species, which then mediates closure of the 5-membered thiazolidine ring. RESULTS: Here we report experiments employing time-resolved crystallography to observe turnover of an isosteric substrate analogue designed to intercept the catalytic pathway at an early stage. Reaction in the crystalline enzyme-substrate complex was initiated by the application of high-pressure oxygen, and subsequent flash freezing allowed an oxygenated product to be trapped, bound at the iron centre. A mechanism for formation of the observed thiocarboxylate product is proposed. CONCLUSIONS: In the absence of its natural reaction partner (the N-H proton of the L-cysteinyl-D-valine amide bond), the proposed hydroperoxide intermediate appears to attack the putative thioaldehyde species directly. These results shed light on the events preceding beta-lactam closure in the IPNS reaction cycle, and enhance our understanding of the mechanism for reaction of the enzyme with its natural substrate.
 +
 
 +
Alternative oxidation by isopenicillin N synthase observed by X-ray diffraction.,Ogle JM, Clifton IJ, Rutledge PJ, Elkins JM, Burzlaff NI, Adlington RM, Roach PL, Baldwin JE Chem Biol. 2001 Dec;8(12):1231-7. PMID:11755401<ref>PMID:11755401</ref>
 +
 
 +
From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
 +
</div>
 +
<div class="pdbe-citations 1hb4" style="background-color:#fffaf0;"></div>
==See Also==
==See Also==
*[[Isopenicillin N synthase|Isopenicillin N synthase]]
*[[Isopenicillin N synthase|Isopenicillin N synthase]]
-
 
+
== References ==
-
==Reference==
+
<references/>
-
<ref group="xtra">PMID:011755401</ref><ref group="xtra">PMID:010537113</ref><ref group="xtra">PMID:009194566</ref><ref group="xtra">PMID:007791906</ref><references group="xtra"/>
+
__TOC__
-
[[Category: Emericella nidulans]]
+
</StructureSection>
-
[[Category: Adlington, R M.]]
+
[[Category: Aspergillus nidulans]]
-
[[Category: Baldwin, J E.]]
+
[[Category: Large Structures]]
-
[[Category: Burzlaff, N I.]]
+
[[Category: Adlington RM]]
-
[[Category: Clifton, I J.]]
+
[[Category: Baldwin JE]]
-
[[Category: Elkins, J M.]]
+
[[Category: Burzlaff NI]]
-
[[Category: Ogle, J M.]]
+
[[Category: Clifton IJ]]
-
[[Category: Roach, P L.]]
+
[[Category: Elkins JM]]
-
[[Category: Rutledge, P J.]]
+
[[Category: Ogle JM]]
-
[[Category: Antibiotic biosynthesis]]
+
[[Category: Roach PL]]
-
[[Category: B-lactam antibiotic]]
+
[[Category: Rutledge PJ]]
-
[[Category: Oxygenase]]
+
-
[[Category: Penicillin biosynthesis]]
+

Current revision

ISOPENICILLIN N SYNTHASE FROM ASPERGILLUS NIDULANS (OXYGEN EXPOSED PRODUCT FROM ANAEROBIC ACOV FE COMPLEX)

PDB ID 1hb4

Drag the structure with the mouse to rotate

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/1hb4"
Personal tools