1ppk

<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>

</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='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>

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== 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>

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<div class="pdbe-citations 1ppk" style="background-color:#fffaf0;"></div>

[[Category: Cbs 340 48]]

[[Category: Penicillopepsin]]

[[Category: James, M N.G]]

[[Category: Strynadka, N C.J]]

[[Category: Hydrolase-hydrolase inhibitor complex]]