PDBsum entry 4mbb

Hydrolase

PDB id: 4mbb

Contents

Protein chain

184 a.a.

Ligands

PO4

Metals

_CL

Waters ×181

PDB id:

4mbb

Name:

Hydrolase

Title:

Cubic crystal form of pir1 dual specificity phosphatase core

Structure:

RNA/rnp complex-1-interacting phosphatase. Chain: a. Fragment: unp residues 29-207. Synonym: dual specificity protein phosphatase 11, phosphatase that interacts with RNA/rnp complex 1. Engineered: yes. Mutation: yes

Source:

Homo sapiens. Human. Organism_taxid: 9606. Gene: dusp11, pir1. Expressed in: escherichia coli. Expression_system_taxid: 469008.

Resolution:

1.85Å R-factor: 0.169 R-free: 0.188

Authors:

R.S.Sankhala,R.K.Lokareddy,G.Cingolani

Key ref:

R.S.Sankhala et al. (2014). Structure of human PIR1, an atypical dual-specificity phosphatase. Biochemistry, 53, 862-871. PubMed id: 24447265 DOI: 10.1021/bi401240x

Date:

19-Aug-13 Release date: 18-Dec-13

Protein chain

O75319  (DUS11_HUMAN) -  RNA/RNP complex-1-interacting phosphatase from Homo sapiens

Seq: 377 a.a.

Struc: 184 a.a.*

* PDB and UniProt seqs differ at 5 residue positions (black crosses)

Enzyme reactions

• Enzyme class: E.C.3.1.3.- - ?????

DOI no: 10.1021/bi401240x

Biochemistry 53:862-871 (2014)

PubMed id: 24447265

Structure of human PIR1, an atypical dual-specificity phosphatase.

R.S.Sankhala, R.K.Lokareddy, G.Cingolani.

ABSTRACT

PIR1 is an atypical dual-specificity phosphatase (DSP) that dephosphorylates RNA with a higher specificity than phosphoproteins. Here we report the atomic structure of a catalytically inactive mutant (C152S) of the human PIR1 phosphatase core (PIR1-core, residues 29-205), refined at 1.20 Å resolution. PIR1-core shares structural similarities with DSPs related to Vaccinia virus VH1 and with RNA 5'-phosphatases such as the baculovirus RNA triphosphatase and the human mRNA capping enzyme. The PIR1 active site cleft is wider and deeper than that of VH1 and contains two bound ions: a phosphate trapped above the catalytic cysteine C152 exemplifies the binding mode expected for the γ-phosphate of RNA, and ∼6 Å away, a chloride ion coordinates the general base R158. Two residues in the PIR1 phosphate-binding loop (P-loop), a histidine (H154) downstream of C152 and an asparagine (N157) preceding R158, make close contacts with the active site phosphate, and their nonaliphatic side chains are essential for phosphatase activity in vitro. These residues are conserved in all RNA 5'-phosphatases that, analogous to PIR1, lack a "general acid" residue. Thus, a deep active site crevice, two active site ions, and conserved P-loop residues stabilizing the γ-phosphate of RNA are defining features of atypical DSPs that specialize in dephosphorylating 5'-RNA.