4MBB

Cubic crystal form of PIR1 dual specificity phosphatase core

Summary for 4MBB

• Entry DOI: 10.2210/pdb4mbb/pdb
• Related: 1I9S 1VHR 1YN9 3CM3
• Descriptor: RNA/RNP complex-1-interacting phosphatase, CHLORIDE ION, PHOSPHATE ION, ... (4 entities in total)
• Functional Keywords: atypical dual specificity phosphatase, pir1-core, rna splicing, helical hairpin, ptp-loop, deep catalytic cleft, phosphate-binding loop (p-loop), acidic loop (wpd-loop), rna phosphatase, dual specificity phosphatase, rna-rnp complex-1, dephosphorylation, nucleus, hydrolase
• Biological source: Homo sapiens (human)
• Cellular location: Nucleus: O75319
• Total number of polymer chains: 1
• Total formula weight: 21607.92

Authors

Sankhala, R.S.,Lokareddy, R.K.,Cingolani, G. (deposition date: 2013-08-19, release date: 2013-12-18, Last modification date: 2023-09-20)

Primary citation

Sankhala, R.S.,Lokareddy, R.K.,Cingolani, G.
Structure of Human PIR1, an Atypical Dual-Specificity Phosphatase.
Biochemistry, 53:862-871, 2014

PubMed 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.

PubMed: 24447265
DOI: 10.1021/bi401240x

Experimental method

X-RAY DIFFRACTION (1.849 Å)