2x1c: Difference between revisions

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[[Image:2x1c.png|left|200px]]


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==The crystal structure of precursor acyl coenzyme A:isopenicillin N acyltransferase from Penicillium chrysogenum==
The line below this paragraph, containing "STRUCTURE_2x1c", creates the "Structure Box" on the page.
<StructureSection load='2x1c' size='340' side='right'caption='[[2x1c]], [[Resolution|resolution]] 1.85&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'>[[2x1c]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/Penicillium_chrysogenum Penicillium chrysogenum]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2X1C OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2X1C 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]] 1.85&#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=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene></td></tr>
{{STRUCTURE_2x1c|  PDB=2x1c  |  SCENE= }}
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=2x1c FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2x1c OCA], [https://pdbe.org/2x1c PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2x1c RCSB], [https://www.ebi.ac.uk/pdbsum/2x1c PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2x1c ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/AATA_PENCH AATA_PENCH] Isopenicillin-N N-acyltransferase; part of the gene cluster that mediates the biosynthesis of penicillin, the world's most important antibiotic (PubMed:2120195, PubMed:2110531, PubMed:1368505). AatA catalyzes the exchange of the alpha-aminoadipyl side chain of isopenicillin N for phenylacetic acid to yield penicillin (PubMed:2120195, PubMed:2110531, PubMed:1368505). This step occurs in the peroxisomal matrix and the penM and paaT transporters are involved in the isopenicillin N and phenylacetic acid import into the peroxisome, respectively (PubMed:23053082). 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 aatA to yield penicillin in the peroxisomal matrix (PubMed:1368505) (Probable).<ref>PMID:1368505</ref> <ref>PMID:2110531</ref> <ref>PMID:2120195</ref> <ref>PMID:23053082</ref> <ref>PMID:1368505</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/x1/2x1c_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=2x1c ConSurf].
<div style="clear:both"></div>
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
Penicillium chrysogenum Acyl coenzyme A:isopenicillin N acyltransferase (AT) performs the last step in the biosynthesis of hydrophobic penicillins, exchanging the hydrophilic side chain of a precursor for various hydrophobic side chains. Like other N-terminal nucleophile hydrolases AT is produced as an inactive precursor that matures upon posttranslational cleavage. The structure of a Cys103Ala precursor mutant shows that maturation is autoproteolytic, initiated by Cys103 cleaving its preceding peptide bond. The crystal structure of the mature enzyme shows that after autoproteolysis residues 92-102 fold outwards, exposing a buried pocket. This pocket is structurally and chemically flexible and can accommodate substrates of different size and polarity. Modeling of a substrate-bound state indicates the residues important for catalysis. Comparison of the proposed autoproteolytic and substrate hydrolysis mechanisms shows that in both events the same catalytic residues are used, but that they perform different roles in catalysis.


===THE CRYSTAL STRUCTURE OF PRECURSOR ACYL COENZYME A:ISOPENICILLIN N ACYLTRANSFERASE FROM PENICILLIUM CHRYSOGENUM===
Structures of an isopenicillin N converting Ntn-hydrolase reveal different catalytic roles for the active site residues of precursor and mature enzyme.,Bokhove M, Yoshida H, Hensgens CM, van der Laan JM, Sutherland JD, Dijkstra BW Structure. 2010 Mar 10;18(3):301-8. PMID:20223213<ref>PMID:20223213</ref>


 
From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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</div>
The line below this paragraph, {{ABSTRACT_PUBMED_20223213}}, adds the Publication Abstract to the page
<div class="pdbe-citations 2x1c" style="background-color:#fffaf0;"></div>
(as it appears on PubMed at http://www.pubmed.gov), where 20223213 is the PubMed ID number.
== References ==
-->
<references/>
{{ABSTRACT_PUBMED_20223213}}
__TOC__
 
</StructureSection>
==About this Structure==
[[Category: Large Structures]]
2X1C is a 4 chains structure with sequences from [http://en.wikipedia.org/wiki/Penicillium_chrysogenum Penicillium chrysogenum]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2X1C OCA].
 
==Reference==
<ref group="xtra">PMID:20223213</ref><references group="xtra"/>
[[Category: Isopenicillin-N N-acyltransferase]]
[[Category: Penicillium chrysogenum]]
[[Category: Penicillium chrysogenum]]
[[Category: Bokhove, M.]]
[[Category: Bokhove M]]
[[Category: Dijkstra, B W.]]
[[Category: Dijkstra BW]]
[[Category: Hensgens, C M.H.]]
[[Category: Hensgens CMH]]
[[Category: Laan, J M.Van Der.]]
[[Category: Sutherland JD]]
[[Category: Sutherland, J D.]]
[[Category: Yoshida H]]
[[Category: Yoshida, H.]]
[[Category: Van der Laan JM]]
[[Category: Acyltransferase]]
[[Category: Antibiotic biosynthesis]]
[[Category: Ntn-hydrolase]]
[[Category: Penicillin biosynthesis]]
[[Category: Transferase]]
[[Category: Zymogen]]
 
''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Wed Mar 24 08:28:33 2010''

Latest revision as of 13:19, 9 May 2024

The crystal structure of precursor acyl coenzyme A:isopenicillin N acyltransferase from Penicillium chrysogenumThe crystal structure of precursor acyl coenzyme A:isopenicillin N acyltransferase from Penicillium chrysogenum

Structural highlights

2x1c is a 4 chain structure with sequence from Penicillium chrysogenum. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:X-ray diffraction, Resolution 1.85Å
Ligands:, ,
Resources:FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

AATA_PENCH Isopenicillin-N N-acyltransferase; part of the gene cluster that mediates the biosynthesis of penicillin, the world's most important antibiotic (PubMed:2120195, PubMed:2110531, PubMed:1368505). AatA catalyzes the exchange of the alpha-aminoadipyl side chain of isopenicillin N for phenylacetic acid to yield penicillin (PubMed:2120195, PubMed:2110531, PubMed:1368505). This step occurs in the peroxisomal matrix and the penM and paaT transporters are involved in the isopenicillin N and phenylacetic acid import into the peroxisome, respectively (PubMed:23053082). 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 aatA to yield penicillin in the peroxisomal matrix (PubMed:1368505) (Probable).[1] [2] [3] [4] [5]

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

Penicillium chrysogenum Acyl coenzyme A:isopenicillin N acyltransferase (AT) performs the last step in the biosynthesis of hydrophobic penicillins, exchanging the hydrophilic side chain of a precursor for various hydrophobic side chains. Like other N-terminal nucleophile hydrolases AT is produced as an inactive precursor that matures upon posttranslational cleavage. The structure of a Cys103Ala precursor mutant shows that maturation is autoproteolytic, initiated by Cys103 cleaving its preceding peptide bond. The crystal structure of the mature enzyme shows that after autoproteolysis residues 92-102 fold outwards, exposing a buried pocket. This pocket is structurally and chemically flexible and can accommodate substrates of different size and polarity. Modeling of a substrate-bound state indicates the residues important for catalysis. Comparison of the proposed autoproteolytic and substrate hydrolysis mechanisms shows that in both events the same catalytic residues are used, but that they perform different roles in catalysis.

Structures of an isopenicillin N converting Ntn-hydrolase reveal different catalytic roles for the active site residues of precursor and mature enzyme.,Bokhove M, Yoshida H, Hensgens CM, van der Laan JM, Sutherland JD, Dijkstra BW Structure. 2010 Mar 10;18(3):301-8. PMID:20223213[6]

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

References

  1. ↑ Smith DJ, Burnham MK, Edwards J, Earl AJ, Turner G. Cloning and heterologous expression of the penicillin biosynthetic gene cluster from penicillum chrysogenum. Biotechnology (N Y). 1990 Jan;8(1):39-41. PMID:1368505 doi:10.1038/nbt0190-39
  2. ↑ Whiteman PA, Abraham EP, Baldwin JE, Fleming MD, Schofield CJ, Sutherland JD, Willis AC. Acyl coenzyme A: 6-aminopenicillanic acid acyltransferase from Penicillium chrysogenum and Aspergillus nidulans. FEBS Lett. 1990 Mar 26;262(2):342-4. PMID:2110531 doi:10.1016/0014-5793(90)80224-7
  3. ↑ Tobin MB, Fleming MD, Skatrud PL, Miller JR. Molecular characterization of the acyl-coenzyme A:isopenicillin N acyltransferase gene (penDE) from Penicillium chrysogenum and Aspergillus nidulans and activity of recombinant enzyme in Escherichia coli. J Bacteriol. 1990 Oct;172(10):5908-14. PMID:2120195 doi:10.1128/jb.172.10.5908-5914.1990
  4. ↑ Fernández-Aguado M, Ullán RV, Teijeira F, Rodríguez-Castro R, Martín JF. The transport of phenylacetic acid across the peroxisomal membrane is mediated by the PaaT protein in Penicillium chrysogenum. Appl Microbiol Biotechnol. 2013 Apr;97(7):3073-84. PMID:23053082 doi:10.1007/s00253-012-4425-1
  5. ↑ Smith DJ, Burnham MK, Edwards J, Earl AJ, Turner G. Cloning and heterologous expression of the penicillin biosynthetic gene cluster from penicillum chrysogenum. Biotechnology (N Y). 1990 Jan;8(1):39-41. PMID:1368505 doi:10.1038/nbt0190-39
  6. ↑ Bokhove M, Yoshida H, Hensgens CM, van der Laan JM, Sutherland JD, Dijkstra BW. Structures of an isopenicillin N converting Ntn-hydrolase reveal different catalytic roles for the active site residues of precursor and mature enzyme. Structure. 2010 Mar 10;18(3):301-8. PMID:20223213 doi:10.1016/j.str.2010.01.005

2x1c, resolution 1.85Å

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