PDBsum entry 4ad9

Hydrolase

PDB id: 4ad9

Contents

Protein chain

(+ 0 more) 288 a.a.

Ligands

EDO ×4

Metals

_ZN ×12

Waters ×1055

PDB id:

4ad9

Name:

Hydrolase

Title:

Crystal structure of human lactb2.

Structure:

Beta-lactamase-like protein 2. Chain: a, b, c, d, e, f. Synonym: lactb2. Engineered: yes

Source:

Homo sapiens. Human. Organism_taxid: 9606. Expressed in: escherichia coli. Expression_system_taxid: 469008. Expression_system_variant: r3-prare2.

Resolution:

2.60Å R-factor: 0.179 R-free: 0.224

Authors:

C.K.Allerston,T.Krojer,B.Shrestha,N.Burgess Brown,R.Chalk,J.M.Elkins, P.Filippakopoulos,A.C.W.Pike,J.R.C.Muniz,M.Vollmar,C.H.Arrowsmith, J.Weigelt,A.Edwards,C.Bountra,F.Von Delft,O.Gileadi

Key ref:

S.Levy et al. (2016). Identification of LACTB2, a metallo-β-lactamase protein, as a human mitochondrial endoribonuclease. Nucleic Acids Res, 44, 1813-1832. PubMed id: 26826708 DOI: 10.1093/nar/gkw050

Date:

22-Dec-11 Release date: 01-Feb-12

Protein chains

Q53H82  (LACB2_HUMAN) -  Endoribonuclease LACTB2 from Homo sapiens

Seq: 288 a.a.

Struc: 288 a.a.

Enzyme reactions

• Enzyme class: E.C.3.1.27.- - ?????

DOI no: 10.1093/nar/gkw050

Nucleic Acids Res 44:1813-1832 (2016)

PubMed id: 26826708

Identification of LACTB2, a metallo-β-lactamase protein, as a human mitochondrial endoribonuclease.

S.Levy, C.K.Allerston, V.Liveanu, M.R.Habib, O.Gileadi, G.Schuster.

ABSTRACT

Post-transcriptional control of mitochondrial gene expression, including the processing and generation of mature transcripts as well as their degradation, is a key regulatory step in gene expression in human mitochondria. Consequently, identification of the proteins responsible for RNA processing and degradation in this organelle is of great importance. The metallo-β-lactamase (MBL) is a candidate protein family that includes ribo- and deoxyribonucleases. In this study, we discovered a function for LACTB2, an orphan MBL protein found in mammalian mitochondria. Solving its crystal structure revealed almost perfect alignment of the MBL domain with CPSF73, as well as to other ribonucleases of the MBL superfamily. Recombinant human LACTB2 displayed robust endoribonuclease activity on ssRNA with a preference for cleavage after purine-pyrimidine sequences. Mutational analysis identified an extended RNA-binding site. Knockdown of LACTB2 in cultured cells caused a moderate but significant accumulation of many mitochondrial transcripts, and its overexpression led to the opposite effect. Furthermore, manipulation of LACTB2 expression resulted in cellular morphological deformation and cell death. Together, this study discovered that LACTB2 is an endoribonuclease that is involved in the turnover of mitochondrial RNA, and is essential for mitochondrial function in human cells.