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-[[Image:1ppm.jpg|left|200px]]
-<!--
-The line below this paragraph, containing "STRUCTURE_1ppm", creates the "Structure Box" on the page.
-You may change the PDB parameter (which sets the PDB file loaded into the applet)
-or the SCENE parameter (which sets the initial scene displayed when the page is loaded),
-or leave the SCENE parameter empty for the default display.
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-{{STRUCTURE_1ppm|  PDB=1ppm  |  SCENE=  }}
-'''CRYSTALLOGRAPHIC ANALYSIS OF TRANSITION-STATE MIMICS BOUND TO PENICILLOPEPSIN: PHOSPHORUS-CONTAINING PEPTIDE ANALOGUES'''
+==CRYSTALLOGRAPHIC ANALYSIS OF TRANSITION-STATE MIMICS BOUND TO PENICILLOPEPSIN: PHOSPHORUS-CONTAINING PEPTIDE ANALOGUES==
+<StructureSection load='1ppm' size='340' side='right'caption='[[1ppm]], [[Resolution|resolution]] 1.70&Aring;' scene=''>
+== Structural highlights ==
+<table><tr><td colspan='2'>[[1ppm]] 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=1PPM OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1PPM 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]] 1.7&#8491;</td></tr>
+<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=0P1:N-[(BENZYLOXY)CARBONYL]-L-ALANYL-N-{(1S)-1-[(R)-[(1R)-1-BENZYL-2-METHOXY-2-OXOETHOXY](HYDROXY)PHOSPHORYL]-3-METHYLBUTYL}-L-ALANINAMIDE'>0P1</scene>, <scene name='pdbligand=ARA:ALPHA-L-ARABINOSE'>ARA</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=1ppm FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1ppm OCA], [https://pdbe.org/1ppm PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1ppm RCSB], [https://www.ebi.ac.uk/pdbsum/1ppm PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1ppm ProSAT]</span></td></tr>
+</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 ==
+[[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/pp/1ppm_consurf.spt"</scriptWhenChecked>
+    <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview03.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=1ppm ConSurf].
+<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)
-==Overview==
+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>
-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)
-==About this Structure==
+From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
-PPM is a [[Single protein]] structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1PPM OCA].
+</div>
+<div class="pdbe-citations 1ppm" style="background-color:#fffaf0;"></div>
-==Reference==
+==See Also==
-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:[http://www.ncbi.nlm.nih.gov/pubmed/1606144 1606144]
+*[[Penicillopepsin|Penicillopepsin]]
-[[Category: Penicillopepsin]]
+*[[Pepsin|Pepsin]]
-[[Category: Single protein]]
+== References ==
-[[Category: Fraser, M E.]]
+<references/>
-[[Category: James, M N.G.]]
+__TOC__
-''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sat May  3 05:20:33 2008''
+</StructureSection>
+[[Category: Large Structures]]
+[[Category: Penicillium janthinellum]]
+[[Category: Fraser ME]]
+[[Category: James MNG]]