1ppk: Difference between revisions

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<StructureSection load='1ppk' size='340' side='right'caption='[[1ppk]], [[Resolution|resolution]] 1.80&Aring;' scene=''>
<StructureSection load='1ppk' size='340' side='right'caption='[[1ppk]], [[Resolution|resolution]] 1.80&Aring;' scene=''>
== Structural highlights ==
== Structural highlights ==
<table><tr><td colspan='2'>[[1ppk]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Cbs_340.48 Cbs 340.48]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1PPK OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1PPK FirstGlance]. <br>
<table><tr><td colspan='2'>[[1ppk]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Penicillium_janthinellum Penicillium janthinellum]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1PPK OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1PPK FirstGlance]. <br>
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=DMF:DIMETHYLFORMAMIDE'>DMF</scene>, <scene name='pdbligand=HSY:ALPHA-L-XYLOPYRANOSE'>HSY</scene>, <scene name='pdbligand=IVV:N-(3-METHYLBUTANOYL)-L-VALYL-N-{(1R)-1-[(R)-(2-ETHOXY-2-OXOETHYL)(HYDROXY)PHOSPHORYL]-3-METHYLBUTYL}-L-VALINAMIDE'>IVV</scene>, <scene name='pdbligand=MAN:ALPHA-D-MANNOSE'>MAN</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene></td></tr>
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.8&#8491;</td></tr>
<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[https://en.wikipedia.org/wiki/Penicillopepsin Penicillopepsin], with EC number [https://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.4.23.20 3.4.23.20] </span></td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=DMF:DIMETHYLFORMAMIDE'>DMF</scene>, <scene name='pdbligand=HSY:ALPHA-L-XYLOPYRANOSE'>HSY</scene>, <scene name='pdbligand=IVV:N-(3-METHYLBUTANOYL)-L-VALYL-N-{(1R)-1-[(R)-(2-ETHOXY-2-OXOETHYL)(HYDROXY)PHOSPHORYL]-3-METHYLBUTYL}-L-VALINAMIDE'>IVV</scene>, <scene name='pdbligand=MAN:ALPHA-D-MANNOSE'>MAN</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=1ppk FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1ppk OCA], [https://pdbe.org/1ppk PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1ppk RCSB], [https://www.ebi.ac.uk/pdbsum/1ppk PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1ppk ProSAT]</span></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=1ppk FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1ppk OCA], [https://pdbe.org/1ppk PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1ppk RCSB], [https://www.ebi.ac.uk/pdbsum/1ppk PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1ppk ProSAT]</span></td></tr>
</table>
</table>
== Function ==
[https://www.uniprot.org/uniprot/PEPA1_PENJA PEPA1_PENJA] Secreted aspartic endopeptidase that allows assimilation of proteinaceous substrates. The scissile peptide bond is attacked by a nucleophilic water molecule activated by two aspartic residues in the active site. Shows a broad primary substrate specificity. Favors hydrophobic residues at the P1 and P1' positions, but can also activate trypsinogen and hydrolyze the B chain of insulin between positions 'Gly-20' and 'Glu-21'.<ref>PMID:4946839</ref>
== Evolutionary Conservation ==
== Evolutionary Conservation ==
[[Image:Consurf_key_small.gif|200px|right]]
[[Image:Consurf_key_small.gif|200px|right]]
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</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=1ppk ConSurf].
</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=1ppk ConSurf].
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<div style="clear:both"></div>
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
The molecular structures of three phosphorus-based peptide inhibitors of aspartyl proteinases complexed with penicillopepsin [1, Iva-L-Val-L-Val-StaPOEt [Iva = isovaleryl, StaP = the phosphinic acid analogue of statine [(S)-4-amino-(S)-3-hydroxy-6-methylheptanoic acid] (IvaVVStaPOEt)]; 2, Iva-L-Val-L-Val-L-LeuP-(O)Phe-OMe [LeuP = the phosphinic acid analogue of L-leucine; (O)Phe = L-3-phenyllactic acid; OMe = methyl ester] [Iva VVLP(O)FOMe]; and 3, Cbz-L-Ala-L-Ala-L-LeuP-(O)-Phe-OMe (Cbz = benzyloxycarbonyl) [CbzAALP(O)FOMe]] have been determined by X-ray crystallography and refined to crystallographic agreement factors, R ( = sigma parallel to F0 magnitude of - Fc parallel to/sigma magnitude of F0), of 0.132, 0.131, and 0.134, respectively. These inhibitors were designed to be structural mimics of the tetrahederal transition-state intermediate encountered during aspartic proteinase catalysis. They are potent inhibitors of penicillopepsin with Ki values of 1, 22 nM; 2, 2.8 nM; and 3, 1600 nM, respectively [Bartlett, P. A., Hanson, J. E., &amp; Giannousis, P. P. (1990) J. Org. Chem. 55, 6268-6274]. All three of these phosphorus-based inhibitors bind virtually identically in the active site of penicillopepsin in a manner that closely approximates that expected for the transition state [James, M. N. G., Sielecki, A.R., Hayakawa, K., &amp; Gelb, M. H. (1992) Biochemistry 31, 3872-3886]. The pro-S oxygen atom of the two phosphonate inhibitors and of the phosphinate group of the StaP inhibitor make very short contact distances (approximately 2.4 A) to the carboxyl oxygen atom, O delta 1, of Asp33 on penicillopepsin. We have interpreted this distance and the stereochemical environment of the carboxyl and phosphonate groups in terms of a hydrogen bond that most probably has a symmetric single-well potential energy function. The pro-R oxygen atom is the recipient of a hydrogen bond from the carboxyl group of Asp213. Thus, we are able to assign a neutral status to Asp213 and a partially negatively charged status to Asp33 with reasonable confidence. Similar very short hydrogen bonds involving the active site glutamic acid residues of thermolysin and carboxypeptidase A and the pro-R oxygen of bound phosphonate inhibitors have been reported [Holden, H. M., Tronrud, D. E., Monzingo, A. F., Weaver, L. H., &amp; Matthews, B. W. (1987) Biochemistry 26, 8542-8553; Kim, H., &amp; Lipscomb, W. N. (1991) Biochemistry 30, 8171-8180].(ABSTRACT TRUNCATED AT 400 WORDS)
Crystallographic analysis of transition-state mimics bound to penicillopepsin: phosphorus-containing peptide analogues.,Fraser ME, Strynadka NC, Bartlett PA, Hanson JE, James MN Biochemistry. 1992 Jun 9;31(22):5201-14. PMID:1606144<ref>PMID:1606144</ref>
From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 1ppk" style="background-color:#fffaf0;"></div>


==See Also==
==See Also==
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__TOC__
__TOC__
</StructureSection>
</StructureSection>
[[Category: Cbs 340 48]]
[[Category: Large Structures]]
[[Category: Large Structures]]
[[Category: Penicillopepsin]]
[[Category: Penicillium janthinellum]]
[[Category: James, M N.G]]
[[Category: James MNG]]
[[Category: Strynadka, N C.J]]
[[Category: Strynadka NCJ]]
[[Category: Acid proteinase]]
[[Category: Hydrolase-hydrolase inhibitor complex]]

Revision as of 08:57, 17 April 2024

CRYSTALLOGRAPHIC ANALYSIS OF TRANSITION STATE MIMICS BOUND TO PENICILLOPEPSIN: PHOSPHOROUS-CONTAINING PEPTIDE ANALOGUESCRYSTALLOGRAPHIC ANALYSIS OF TRANSITION STATE MIMICS BOUND TO PENICILLOPEPSIN: PHOSPHOROUS-CONTAINING PEPTIDE ANALOGUES

Structural highlights

1ppk is a 1 chain structure with sequence from Penicillium janthinellum. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:X-ray diffraction, Resolution 1.8Å
Ligands:, , , ,
Resources:FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

PEPA1_PENJA Secreted aspartic endopeptidase that allows assimilation of proteinaceous substrates. The scissile peptide bond is attacked by a nucleophilic water molecule activated by two aspartic residues in the active site. Shows a broad primary substrate specificity. Favors hydrophobic residues at the P1 and P1' positions, but can also activate trypsinogen and hydrolyze the B chain of insulin between positions 'Gly-20' and 'Glu-21'.[1]

Evolutionary Conservation

Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.

See Also

References

  1. ↑ Mains G, Takahashi M, Sodek J, Hofmann T. The specificity of penicillopepsin. Can J Biochem. 1971 Oct;49(10):1134-49. PMID:4946839 doi:10.1139/o71-164

1ppk, resolution 1.80Å

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