1ppk: Difference between revisions
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[[Image:1ppk.gif|left|200px]] | [[Image:1ppk.gif|left|200px]] | ||
'''CRYSTALLOGRAPHIC ANALYSIS OF TRANSITION STATE MIMICS BOUND TO PENICILLOPEPSIN: PHOSPHOROUS-CONTAINING PEPTIDE ANALOGUES''' | {{Structure | ||
|PDB= 1ppk |SIZE=350|CAPTION= <scene name='initialview01'>1ppk</scene>, resolution 1.8Å | |||
|SITE= | |||
|LIGAND= <scene name='pdbligand=MAN:ALPHA-D-MANNOSE'>MAN</scene>, <scene name='pdbligand=XYS:XYLOPYRANOSE'>XYS</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene>, <scene name='pdbligand=ETH:ETHYL+GROUP'>ETH</scene> and <scene name='pdbligand=DMF:DIMETHYLFORMAMIDE'>DMF</scene> | |||
|ACTIVITY= [http://en.wikipedia.org/wiki/Penicillopepsin Penicillopepsin], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.4.23.20 3.4.23.20] | |||
|GENE= | |||
}} | |||
'''CRYSTALLOGRAPHIC ANALYSIS OF TRANSITION STATE MIMICS BOUND TO PENICILLOPEPSIN: PHOSPHOROUS-CONTAINING PEPTIDE ANALOGUES''' | |||
==Overview== | ==Overview== | ||
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==About this Structure== | ==About this Structure== | ||
1PPK is a [ | 1PPK is a [[Single protein]] structure of sequence from [http://en.wikipedia.org/wiki/ ]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1PPK OCA]. | ||
==Reference== | ==Reference== | ||
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:// | 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] | ||
[[Category: Penicillopepsin]] | [[Category: Penicillopepsin]] | ||
[[Category: Single protein]] | [[Category: Single protein]] | ||
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[[Category: hydrolase(acid proteinase)]] | [[Category: hydrolase(acid proteinase)]] | ||
''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Mar 20 13:27:19 2008'' | ||
Revision as of 14:27, 20 March 2008
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| , resolution 1.8Å | |||||||
|---|---|---|---|---|---|---|---|
| Ligands: | , , , and | ||||||
| Activity: | Penicillopepsin, with EC number 3.4.23.20 | ||||||
| Coordinates: | save as pdb, mmCIF, xml | ||||||
CRYSTALLOGRAPHIC ANALYSIS OF TRANSITION STATE MIMICS BOUND TO PENICILLOPEPSIN: PHOSPHOROUS-CONTAINING PEPTIDE ANALOGUES
OverviewOverview
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., & 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., & 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., & Matthews, B. W. (1987) Biochemistry 26, 8542-8553; Kim, H., & Lipscomb, W. N. (1991) Biochemistry 30, 8171-8180].(ABSTRACT TRUNCATED AT 400 WORDS)
About this StructureAbout this Structure
1PPK is a Single protein structure of sequence from [1]. Full crystallographic information is available from OCA.
ReferenceReference
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
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