PDBsum entry 1trn

Hydrolase (serine proteinase)

PDB id: 1trn

Contents

Protein chain

224 a.a. *

Ligands

ISP ×2

Waters ×301

* Residue conservation analysis

PDB id:

1trn

Name:

Hydrolase (serine proteinase)

Title:

Crystal structure of human trypsin 1: unexpected phosphorylation of tyrosine 151

Structure:

Trypsin. Chain: a, b. Engineered: yes

Source:

Homo sapiens. Human. Organism_taxid: 9606

Biol. unit:

Tetramer (from PQS)

Resolution:

2.20Å R-factor: 0.177

Authors:

C.Gaboriaud,J.C.Fontecilla-Camps

Key ref:

C.Gaboriaud et al. (1996). Crystal structure of human trypsin 1: unexpected phosphorylation of Tyr151. J Mol Biol, 259, 995. PubMed id: 8683601 DOI: 10.1006/jmbi.1996.0376

Date:

16-Mar-95 Release date: 03-Jun-95

Protein chains

P07477  (TRY1_HUMAN) -  Serine protease 1 from Homo sapiens

Seq: 247 a.a.

Struc: 224 a.a.

Enzyme reactions

• Enzyme class: E.C.3.4.21.4 - trypsin.
• Reaction: Preferential cleavage: Arg-|-Xaa, Lys-|-Xaa.

DOI no: 10.1006/jmbi.1996.0376

J Mol Biol 259:995 (1996)

PubMed id: 8683601

Crystal structure of human trypsin 1: unexpected phosphorylation of Tyr151.

C.Gaboriaud, L.Serre, O.Guy-Crotte, E.Forest, J.C.Fontecilla-Camps.

ABSTRACT

The X-ray structure of human trypsin 1 has been determined in the presence of diisopropyl-phosphofluoridate by the molecular replacement method and refined at a resolution of 2.2 A to an R-factor of 18%. Crystals belong to the space group P4, with two independent molecules in the asymmetric unit packing as crystallographic tetramers. This study was performed in order to seek possible structural peculiarities of human trypsin 1, suggested by some striking differences in its biochemical behavior as compared to other trypsins of mammalian species. Its fold is, in fact, very similar to those of the bovine, rat and porcine trypsins, with root-mean-square differences in the 0.4 to 0.6 A range for all 223 C alpha positions. The most unexpected feature of the human trypsin 1 structure is in the phosphorylated state of tyrosine residue 151 in the present X-ray study. This feature was confirmed by mass spectrometry on the same inhibited sample and also on the native enzyme. This phosphorylation strengthens the outstanding clustering of highly negative or highly positive electrostatic surface potentials. The peculiar inhibitory behaviour of pancreatic secretory trypsin inhibitors of the Kazal type on this enzyme is discussed as a possible consequence of these properties. A charged surface loop has also been interpreted as an epitope site recognised by a monoclonal antibody specific to human trypsin 1.

Selected figure(s)

Figure 6.
Figure 6. Stereo view of the (2Fo - Fc) electron density map around the active site superposed on the refined model containing the serine-bound diisopropyl phosphate. The electron density map was contoured at the 1s level. Hydrogen bonds are drawn with broken lines.

Figure 7.
Figure 7. Stereo view of the (2Fo - Fc) electron density map around the phosphotyrosine residue 151, superposed on the refined model. The electron density map was contoured at the 1s level. All residues within 5 Å of the Tyr151 hydroxyl group are displayed.

The above figures are reprinted by permission from Elsevier: J Mol Biol (1996, 259, 995-0) copyright 1996.

Figures were selected by an automated process.