PDBsum entry 4j7n

Hydrolase

PDB id: 4j7n

Contents

Protein chain

358 a.a.

Ligands

GTG ×2

9MG

EDO ×2

Waters ×442

PDB id:

4j7n

Name:

Hydrolase

Title:

Crystal structure of mouse dxo in complex with m7gpppg cap

Structure:

Protein dom3z. Chain: a. Synonym: dom-3 homolog z, dxo. Engineered: yes

Source:

Mus musculus. Mouse. Organism_taxid: 10090. Gene: dom3z, ng6. Expressed in: escherichia coli. Expression_system_taxid: 562

Resolution:

1.50Å R-factor: 0.172 R-free: 0.200

Authors:

T.Kilic,J.H.Chang,L.Tong

Key ref:

X.Jiao et al. (2013). A mammalian pre-mRNA 5' end capping quality control mechanism and an unexpected link of capping to pre-mRNA processing. Mol Cell, 50, 104-115. PubMed id: 23523372 DOI: 10.1016/j.molcel.2013.02.017

Date:

13-Feb-13 Release date: 27-Mar-13

Protein chain

O70348  (DXO_MOUSE) -  Decapping and exoribonuclease protein from Mus musculus

Seq: 397 a.a.

Struc: 358 a.a.

Enzyme reactions

• Enzyme class 1: E.C.3.1.13.- - ?????
• Enzyme class 2: E.C.3.6.1.- - ?????

Note, where more than one E.C. class is given (as above), each may correspond to a different protein domain or, in the case of polyprotein precursors, to a different mature protein.

DOI no: 10.1016/j.molcel.2013.02.017

Mol Cell 50:104-115 (2013)

PubMed id: 23523372

A mammalian pre-mRNA 5' end capping quality control mechanism and an unexpected link of capping to pre-mRNA processing.

X.Jiao, J.H.Chang, T.Kilic, L.Tong, M.Kiledjian.

ABSTRACT

Recently, we reported that two homologous yeast proteins, Rai1 and Dxo1, function in a quality control mechanism to clear cells of incompletely 5' end-capped messenger RNAs (mRNAs). Here, we report that their mammalian homolog, Dom3Z (referred to as DXO), possesses pyrophosphohydrolase, decapping, and 5'-to-3' exoribonuclease activities. Surprisingly, we found that DXO preferentially degrades defectively capped pre-mRNAs in cells. Additional studies show that incompletely capped pre-mRNAs are inefficiently spliced at all introns, a fact that contrasts with current understanding, and are also poorly cleaved for polyadenylation. Crystal structures of DXO in complex with substrate mimic and products at a resolution of up to 1.5Å provide elegant insights into the catalytic mechanism and molecular basis for their three apparently distinct activities. Our data reveal a pre-mRNA 5' end capping quality control mechanism in mammalian cells, indicating DXO as the central player for this mechanism, and demonstrate an unexpected intimate link between proper 5' end capping and subsequent pre-mRNA processing.