1oc1: Difference between revisions

From Proteopedia
Jump to navigation Jump to search
← Older edit
No edit summary
No edit summary
 
(20 intermediate revisions by the same user not shown)
Line 1: Line 1:
[[Image:1oc1.gif|left|200px]]<br />
<applet load="1oc1" size="450" color="white" frame="true" align="right" spinBox="true"
caption="1oc1, resolution 2.20&Aring;" />
'''ISOPENICILLIN N SYNTHASE AMINOADIPOYL-CYSTEINYL-AMINOBUTYRATE-FE COMPLEX'''<br />


==Overview==
==ISOPENICILLIN N SYNTHASE aminoadipoyl-cysteinyl-aminobutyrate-FE COMPLEX==
Isopenicillin N synthase (IPNS) is a non-haem iron(II) oxidase which, catalyses the biosynthesis of isopenicillin N from the tripeptide, delta-(L-alpha-aminoadipoyl)-L-cysteinyl-D-valine (ACV). Herein we report, crystallographic studies to investigate the reaction of IPNS with the, truncated substrate analogue, delta-(L-alpha-aminoadipoyl)-L-cysteinyl-D-alpha-aminobutyrate (ACAb). It, has been reported previously that this analogue gives rise to three, beta-lactam products when incubated with IPNS: two methyl penams and a, cepham. Crystal structures of the IPNS-Fe(II)-ACAb and IPNS-Fe(II)-ACAb-NO, complexes have now been solved and are reported herein. These structures, and modelling studies based on them shed light on the diminished product, selectivity shown by IPNS in its reaction with ACAb and further, rationalize the presence of certain key residues at the IPNS active site.
<StructureSection load='1oc1' size='340' side='right'caption='[[1oc1]], [[Resolution|resolution]] 2.20&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[1oc1]] 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=1OC1 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1OC1 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]] 2.2&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=ASV:DELTA-(L-ALPHA-AMINOADIPOYL)-L-CYSTEINYL-D-VINYLGLYCINE'>ASV</scene>, <scene name='pdbligand=FE2:FE+(II)+ION'>FE2</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=1oc1 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1oc1 OCA], [https://pdbe.org/1oc1 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1oc1 RCSB], [https://www.ebi.ac.uk/pdbsum/1oc1 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1oc1 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/oc/1oc1_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=1oc1 ConSurf].
<div style="clear:both"></div>
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
Isopenicillin N synthase (IPNS) is a non-haem iron(II) oxidase which catalyses the biosynthesis of isopenicillin N from the tripeptide delta-(L-alpha-aminoadipoyl)-L-cysteinyl-D-valine (ACV). Herein we report crystallographic studies to investigate the reaction of IPNS with the truncated substrate analogue delta-(L-alpha-aminoadipoyl)-L-cysteinyl-D-alpha-aminobutyrate (ACAb). It has been reported previously that this analogue gives rise to three beta-lactam products when incubated with IPNS: two methyl penams and a cepham. Crystal structures of the IPNS-Fe(II)-ACAb and IPNS-Fe(II)-ACAb-NO complexes have now been solved and are reported herein. These structures and modelling studies based on them shed light on the diminished product selectivity shown by IPNS in its reaction with ACAb and further rationalize the presence of certain key residues at the IPNS active site.


==About this Structure==
Structural studies on the reaction of isopenicillin N synthase with the substrate analogue delta-(l-alpha-aminoadipoyl)-l-cysteinyl-d-alpha-aminobutyrate.,Long AJ, Clifton IJ, Roach PL, Baldwin JE, Schofield CJ, Rutledge PJ Biochem J. 2003 Jun 15;372(Pt 3):687-93. PMID:12622704<ref>PMID:12622704</ref>
1OC1 is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Emericella_nidulans Emericella nidulans] with FE2, SO4 and ASV as [http://en.wikipedia.org/wiki/ligands ligands]. Structure known Active Site: AC1. Full crystallographic information is available from [http://ispc.weizmann.ac.il/oca-bin/ocashort?id=1OC1 OCA].


==Reference==
From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
Structural studies on the reaction of isopenicillin N synthase with the substrate analogue delta-(l-alpha-aminoadipoyl)-l-cysteinyl-d-alpha-aminobutyrate., Long AJ, Clifton IJ, Roach PL, Baldwin JE, Schofield CJ, Rutledge PJ, Biochem J. 2003 Jun 15;372(Pt 3):687-93. PMID:[http://ispc.weizmann.ac.il//pmbin/getpm?pmid=12622704 12622704]
</div>
[[Category: Emericella nidulans]]
<div class="pdbe-citations 1oc1" style="background-color:#fffaf0;"></div>
[[Category: Single protein]]
[[Category: Baldwin, J.E.]]
[[Category: Clifton, I.J.]]
[[Category: Long, A.J.]]
[[Category: Roach, P.L.]]
[[Category: Rutledge, P.J.]]
[[Category: Schofield, C.J.]]
[[Category: ASV]]
[[Category: FE2]]
[[Category: SO4]]
[[Category: b-lactam antibiotic]]
[[Category: oxygenase]]
[[Category: penicillin biosynthesis]]


''Page seeded by [http://ispc.weizmann.ac.il/oca OCA ] on Mon Nov  5 15:34:12 2007''
==See Also==
*[[Isopenicillin N synthase|Isopenicillin N synthase]]
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Aspergillus nidulans]]
[[Category: Large Structures]]
[[Category: Baldwin JE]]
[[Category: Clifton IJ]]
[[Category: Long AJ]]
[[Category: Roach PL]]
[[Category: Rutledge PJ]]
[[Category: Schofield CJ]]

Latest revision as of 15:34, 13 December 2023

ISOPENICILLIN N SYNTHASE aminoadipoyl-cysteinyl-aminobutyrate-FE COMPLEXISOPENICILLIN N SYNTHASE aminoadipoyl-cysteinyl-aminobutyrate-FE COMPLEX

Structural highlights

1oc1 is a 1 chain structure with sequence from Aspergillus nidulans. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:X-ray diffraction, Resolution 2.2Å
Ligands:, ,
Resources:FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

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][1] [2] [3]

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

Isopenicillin N synthase (IPNS) is a non-haem iron(II) oxidase which catalyses the biosynthesis of isopenicillin N from the tripeptide delta-(L-alpha-aminoadipoyl)-L-cysteinyl-D-valine (ACV). Herein we report crystallographic studies to investigate the reaction of IPNS with the truncated substrate analogue delta-(L-alpha-aminoadipoyl)-L-cysteinyl-D-alpha-aminobutyrate (ACAb). It has been reported previously that this analogue gives rise to three beta-lactam products when incubated with IPNS: two methyl penams and a cepham. Crystal structures of the IPNS-Fe(II)-ACAb and IPNS-Fe(II)-ACAb-NO complexes have now been solved and are reported herein. These structures and modelling studies based on them shed light on the diminished product selectivity shown by IPNS in its reaction with ACAb and further rationalize the presence of certain key residues at the IPNS active site.

Structural studies on the reaction of isopenicillin N synthase with the substrate analogue delta-(l-alpha-aminoadipoyl)-l-cysteinyl-d-alpha-aminobutyrate.,Long AJ, Clifton IJ, Roach PL, Baldwin JE, Schofield CJ, Rutledge PJ Biochem J. 2003 Jun 15;372(Pt 3):687-93. PMID:12622704[4]

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

See Also

References

  1. ↑ Ogle JM, Clifton IJ, Rutledge PJ, Elkins JM, Burzlaff NI, Adlington RM, Roach PL, Baldwin JE. Alternative oxidation by isopenicillin N synthase observed by X-ray diffraction. Chem Biol. 2001 Dec;8(12):1231-7. PMID:11755401
  2. ↑ McNeill LA, Brown TJN, Sami M, Clifton IJ, Burzlaff NI, Claridge TDW, Adlington RM, Baldwin JE, Rutledge PJ, Schofield CJ. Terminally Truncated Isopenicillin N Synthase Generates a Dithioester Product: Evidence for a Thioaldehyde Intermediate during Catalysis and a New Mode of Reaction for Non-Heme Iron Oxidases. Chemistry. 2017 Sep 18;23(52):12815-12824. doi: 10.1002/chem.201701592. Epub 2017, Aug 21. PMID:28703303 doi:http://dx.doi.org/10.1002/chem.201701592
  3. ↑ Ramon D, Carramolino L, Patino C, Sanchez F, Penalva MA. Cloning and characterization of the isopenicillin N synthetase gene mediating the formation of the beta-lactam ring in Aspergillus nidulans. Gene. 1987;57(2-3):171-81. doi: 10.1016/0378-1119(87)90120-x. PMID:3319778 doi:http://dx.doi.org/10.1016/0378-1119(87)90120-x
  4. ↑ Long AJ, Clifton IJ, Roach PL, Baldwin JE, Schofield CJ, Rutledge PJ. Structural studies on the reaction of isopenicillin N synthase with the substrate analogue delta-(l-alpha-aminoadipoyl)-l-cysteinyl-d-alpha-aminobutyrate. Biochem J. 2003 Jun 15;372(Pt 3):687-93. PMID:12622704 doi:10.1042/BJ20021627

1oc1, resolution 2.20Å

Drag the structure with the mouse to rotate

Proteopedia Page Contributors and Editors (what is this?)Proteopedia Page Contributors and Editors (what is this?)

OCA
Retrieved from "https://proteopedia.openfox.io/wiki/index.php?title=1oc1&oldid=3981797"