PDBsum entry 1pip

Hydrolase/hydrolase inhibitor

PDB id: 1pip

Contents

Protein chain

212 a.a. *

Ligands

ZKO-VAL-VAL-ALA-ALA-NIT

* Residue conservation analysis

PDB id:

1pip

Name:

Hydrolase/hydrolase inhibitor

Title:

Crystal structure of papain-succinyl-gln-val-val-ala-ala-p- nitroanilide complex at 1.7 angstroms resolution: noncovalent binding mode of a common sequence of endogenous thiol protease inhibitors

Structure:

Papain. Chain: a. Synonym: papaya proteinase i,ppi. Engineered: yes. Succinyl-gln-val-val-ala-ala-p-nitroanilide. Chain: b. Engineered: yes

Source:

Carica papaya. Papaya. Organism_taxid: 3649. Synthetic: yes

Biol. unit:

Dimer (from PQS)

Resolution:

1.70Å R-factor: 0.196

Authors:

A.Yamamoto,K.Tomoo,M.Doi,H.Ohishi,M.Inoue,T.Ishida,D.Yamamoto, S.Tsuboi,H.Okamoto,Y.Okada

Key ref:

A.Yamamoto et al. (1992). Crystal structure of papain-succinyl-Gln-Val-Val-Ala-Ala-p-nitroanilide complex at 1.7-A resolution: noncovalent binding mode of a common sequence of endogenous thiol protease inhibitors. Biochemistry, 31, 11305-11309. PubMed id: 1445868 DOI: 10.1021/bi00161a007

Date:

03-Oct-92 Release date: 31-Oct-93

Protein chain

P00784  (PAPA1_CARPA) -  Papain from Carica papaya

Seq: 345 a.a.

Struc: 212 a.a.*

* PDB and UniProt seqs differ at 3 residue positions (black crosses)

Enzyme reactions

• Enzyme class: E.C.3.4.22.2 - papain.
• Reaction: Hydrolysis of proteins with broad specificity for peptide bonds, with preference for a residue bearing a large hydrophobic sidechain at the P2 position. Does not accept Val at P1'.

DOI no: 10.1021/bi00161a007

Biochemistry 31:11305-11309 (1992)

PubMed id: 1445868

Crystal structure of papain-succinyl-Gln-Val-Val-Ala-Ala-p-nitroanilide complex at 1.7-A resolution: noncovalent binding mode of a common sequence of endogenous thiol protease inhibitors.

A.Yamamoto, K.Tomoo, M.Doi, H.Ohishi, M.Inoue, T.Ishida, D.Yamamoto, S.Tsuboi, H.Okamoto, Y.Okada.

ABSTRACT

Succinyl-Gln-Val-Val-Ala-Ala-p-nitroanilide corresponding to a common sequence of endogenous thiol protease inhibitors is a noncompetitive reversible inhibitor of papain. In order to elucidate the binding mode of the inhibitor at the atomic level, its complex with papain was crystallized at ca. pH 7.0 using the hanging drop method, and the crystal structure was analyzed at 1.7-A resolution. The crystal has space group P2(1)2(1)2(1), with a = 43.09, b = 102.32, c = 49.69 A, and Z = 4. A total of 47,215 observed reflections were collected on the imaging plates using the same single crystal, and 19,833 unique reflections with Fo > sigma (Fo) were used for structure determination and refinement. The papain structure was determined by use of the atomic coordinates of papain previously reported, and then refined by the X-PLOR program. The inhibitor molecule was located on a difference Fourier map and fitted into the electron density with the aid of computer graphics. The complex structure was finally refined to R = 19.6% including 118 solvent molecules. The X-ray analysis of the complex crystal shows that the inhibitor is located at the R-domain side, not in the center of the binding site created by the R- and L-domains of papain. Such a binding mode of the inhibitor explains well the biological behavior that the inhibitor exhibits against papain. Comparison with the structure of papain-stefin B complex indicates that the structure of the Gln-Val-Val-Ala-Gly sequence itself is not necessarily the essential requisite for inhibitory activity.(ABSTRACT TRUNCATED AT 250 WORDS)