1QRP

Human pepsin 3A in complex with a phosphonate inhibitor IVA-VAL-VAL-LEU(P)-(O)PHE-ALA-ALA-OME

Summary for 1QRP

• Entry DOI: 10.2210/pdb1qrp/pdb
• Related PRD ID: PRD_000657
• Descriptor: PEPSIN 3A, methyl N-[(2S)-2-({(S)-hydroxy[(1R)-3-methyl-1-{[N-(3-methylbutanoyl)-L-valyl-L-valyl]amino}butyl]phosphoryl}oxy)-3-phenylpropanoyl]-L-alanyl-L-alaninate (3 entities in total)
• Functional Keywords: aspartic proteinase, phosphonate inhibitor, transition state analogue, hydrolase-hydrolase inhibitor complex, hydrolase/hydrolase inhibitor
• Biological source: Homo sapiens (human)
• Total number of polymer chains: 1
• Total formula weight: 35385.75

Authors

Fujinaga, M.,Cherney, M.M.,Tarasova, N.I.,Bartlett, P.A.,Hanson, J.E.,James, M.N.G. (deposition date: 1999-06-15, release date: 1999-06-18, Last modification date: 2024-10-16)

Primary citation

Fujinaga, M.,Cherney, M.M.,Tarasova, N.I.,Bartlett, P.A.,Hanson, J.E.,James, M.N.
Structural study of the complex between human pepsin and a phosphorus-containing peptidic -transition-state analog.
Acta Crystallogr.,Sect.D, 56:272-279, 2000

PubMed Abstract: The refined crystal structure of the complex between human pepsin and a synthetic phosphonate inhibitor, Iva-Val-Val-Leu(P)-(O)Phe-Ala-Ala-OMe [Iva = isovaleryl, Leu(P) = the phosphinic acid analog of L-leucine, (O)Phe = L-3-phenyllactic acid, OMe = methyl ester], is presented. The structure was refined using diffraction data between 30 and 1.96 A resolution to a final R factor ( summation operator| |F(o)| - |F(c)| | / summation operator|F(o)|, where |F(o)| and |F(c)| are the observed and calculated structure-factor amplitudes, respectively) of 20.0%. The interactions of the inhibitor with the enzyme show the locations of the binding sites on the enzyme from S4 to S3'. Modeling of the inhibitor binding to porcine pepsin shows very similar binding sites, except at S4. Comparison of the complex structure with the structures of related inhibitors bound to penicillopepsin helps to rationalize the observed differences in the binding constants. The convergence of reaction mechanisms and geometries in different families of proteinases is also discussed.

PubMed: 10713513
DOI: 10.1107/S0907444999016376

Experimental method

X-RAY DIFFRACTION (1.96 Å)