PDBsum entry 4q80

Hydrolase/hydrolase inhibitor

PDB id: 4q80

Contents

Protein chains

233 a.a.

Ligands

NAG-NAG ×3

NAG

2YS ×2

PDB id:

4q80

Name:

Hydrolase/hydrolase inhibitor

Title:

Neutrophil serine protease 4 (prss57) with val-leu-lys- chloromethylketone (vlk-cmk)

Structure:

Serine protease 57. Chain: a, b. Synonym: serine protease 1-like protein 1. Engineered: yes

Source:

Homo sapiens. Human. Organism_taxid: 9606. Gene: prss57, prssl1, unq782/pro1599. Expressed in: spodoptera frugiperda. Expression_system_taxid: 7108

Resolution:

3.07Å R-factor: 0.188 R-free: 0.240

Authors:

C.Eigenbrot,S.J.Lin,K.C.Dong

Key ref:

S.J.Lin et al. (2014). Structures of neutrophil serine protease 4 reveal an unusual mechanism of substrate recognition by a trypsin-fold protease. Structure, 22, 1333-1340. PubMed id: 25156428 DOI: 10.1016/j.str.2014.07.008

Date:

25-Apr-14 Release date: 03-Sep-14

Protein chains

Q6UWY2  (PRS57_HUMAN) -  Serine protease 57 from Homo sapiens

Seq: 283 a.a.

Struc: 233 a.a.*

* PDB and UniProt seqs differ at 1 residue position (black cross)

Enzyme reactions

• Enzyme class: E.C.3.4.21.- - ?????

DOI no: 10.1016/j.str.2014.07.008

Structure 22:1333-1340 (2014)

PubMed id: 25156428

Structures of neutrophil serine protease 4 reveal an unusual mechanism of substrate recognition by a trypsin-fold protease.

S.J.Lin, K.C.Dong, C.Eigenbrot, M.van Lookeren Campagne, D.Kirchhofer.

ABSTRACT

Trypsin-fold proteases, the largest mammalian protease family, are classified by their primary substrate specificity into one of three categories, trypsin-like, chymotrypsin-like, and elastase-like, based on key structural features of their active site. However, the recently discovered neutrophil serine protease 4 (NSP4, also known as PRSS57) presents a paradox: NSP4 exhibits a trypsin-like specificity for cleaving substrates after arginine residues, but it bears elastase-like specificity determining residues in the active site. Here we show that NSP4 has a fully occluded S1 pocket and that the substrate P1-arginine adopts a noncanonical "up" conformation stabilized by a solvent-exposed H-bond network. This uncommon arrangement, conserved in all NSP4 orthologs, enables NSP4 to process substrates after both arginine as well as post-translationally modified arginine residues, such as methylarginine and citrulline. These findings establish a distinct paradigm for substrate recognition by a trypsin-fold protease and provide insights into the function of NSP4.