tRNase Z Catalysis and Conserved Residues on the Carboxy Side of the His Cluster

Karkashon, Shay; Hopkinson, and Angela; Levinger, Louis

doi:10.1021/bi700578v

Cited by 19 publications

(38 citation statements)

References 28 publications

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“…In addition, the brr5-1 phenotype in yeast, a cold sensitive mutant that exhibits defects in cleavage and polyadenylation [99], is caused by a single-site mutation, A407T [115], that is located next to this His residue in Brr5p/Ysh1p. The functional importance of this His-Glu pair is also confirmed in RNase Z [116].…”

Section: Cpsf-73 (Brr5p/ysh1p)mentioning

confidence: 71%

Protein factors in pre-mRNA 3′-end processing

Mandel

Bai

Tong

2007

Cell. Mol. Life Sci.

357

482

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Most eukaryotic mRNA precursors (pre-mRNAs) must undergo extensive processing, including cleavage and polyadenylation at the 3′-end. Processing at the 3′-end is controlled by sequence elements in the pre-mRNA (cis elements) as well as protein factors. Despite the seeming biochemical simplicity of the processing reactions, more than 14 proteins have been identified for the mammalian complex, and more than 20 proteins have been identified for the yeast complex. The 3′-end processing machinery also has important roles in transcription and splicing. The mammalian machinery contains several sub-complexes, including cleavage and polyadenylation specificity factor (CPSF), cleavage stimulation factor (CstF), cleavage factor I (CF I m ), and cleavage factor II (CF II m ). Additional protein factors include poly(A) polymerase (PAP), poly(A) binding protein (PABP), symplekin, and the C-terminal domain (CTD) of RNA polymerase II largest subunit. The yeast machinery includes cleavage factor IA (CF IA), cleavage factor IB (CF IB), and cleavage and polyadenylation factor (CPF).

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Section: Cpsf-73 (Brr5p/ysh1p)mentioning

confidence: 71%

Protein factors in pre-mRNA 3′-end processing

Mandel

Bai

Tong

2007

Cell. Mol. Life Sci.

357

482

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“…The (S)-malate complex also reveals a potential role for His 200 in stabilizing negative charge on a phosphodiester substrate. The large decreases in k cat upon mutation of this residue in these enzymes (17,34,43) indicate that most of this interaction with a phosphodiester substrate takes place in the transition state. This might arise from stabilization of increasing negative charge development on the nonbridging oxygens in a phosphorane transition state or general acid-catalyzed proton transfer to the leaving group oxygen.…”

Section: Discussionmentioning

confidence: 99%

Structure of PhnP, a Phosphodiesterase of the Carbon-Phosphorus Lyase Pathway for Phosphonate Degradation

Podzelinska

Wathier

et al. 2009

Journal of Biological Chemistry

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Carbon-phosphorus lyase is a multienzyme system encoded by the phn operon that enables bacteria to metabolize organophosphonates when the preferred nutrient, inorganic phosphate, is scarce. One of the enzymes encoded by this operon, PhnP, is predicted by sequence homology to be a metal-dependent hydrolase of the ␤-lactamase superfamily. Screening with a wide array of hydrolytically sensitive substrates indicated that PhnP is an enzyme with phosphodiesterase activity, having the greatest specificity toward bis(pnitrophenyl)phosphate and 2,3-cyclic nucleotides. No activity was observed toward RNA. The metal ion dependence of PhnP with bis(p-nitrophenyl)phosphate as substrate revealed a distinct preference for Mn 2؉ and Ni 2؉ for catalysis, whereas Zn 2؉ afforded poor activity. The three-dimensional structure of PhnP was solved by x-ray crystallography to 1.4 Å resolution. The overall fold of PhnP is very similar to that of the tRNase Z endonucleases but lacks the long exosite module used by these enzymes to bind their tRNA substrates. The active site of PhnP contains what are probably two Mn 2؉ions surrounded by an array of active site residues that are identical to those observed in the tRNase Z enzymes. A second, remote Zn 2؉ binding site is also observed, composed of a set of cysteine and histidine residues that are strictly conserved in the PhnP family. This second metal ion site appears to stabilize a structural motif.

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“…tRNase Z and CPSF-73 (the pre-mRNA 3' end endonuclease 33 ) are both members of the β-lactamase superfamily of metal-dependent hydrolases, 34,35 and their metal-binding and active sites are virtually superimposable. 33,36,37 The active site of CPSF-73 is covered by a large flap (the β-CASP region 33 ) and a battalion of accessory proteins is required for cleavage, presumably to recognize the cleavage site, open the flap and activate the endonuclease.…”

Section: Introductionmentioning

confidence: 99%

Pathogenesis-related mutations in the T-loops of human mitochondrial tRNAs affect 3′ end processing and tRNA structure

Levinger

Serjanov²

2012

RNA Biology

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Numerous mutations in the mitochondrial genome are associated with maternally transmitted diseases and syndromes that affect muscle and other high energy-demand tissues. The mitochondrial genome encodes 13 polypeptides, 2 rRNAs and 22 interspersed tRNAs via long bidirectional polycistronic primary transcripts, requiring precise excision of the tRNAs. Despite making up only~10% of the mitochondrial genome, tRNA genes harbor most of the pathogenesis-related mutations. tRNase Z endonucleolytically removes the pre-tRNA 3' trailer. The flexible arm of tRNase Z recognizes and binds the elbow (including the T-loop) of pre-tRNA. Pathogenesis-related T-loop mutations in mitochondrial tRNAs could thus affect tRNA structure, reduce tRNase Z binding and 3' processing, and consequently slow mitochondrial protein synthesis. Here we inspect the effects of pathogenesis-related mutations in the T-loops of mitochondrial tRNAs on pretRNA structure and tRNase Z processing. Increases in K M arising from 59A . G substitutions in mitochondrial tRNA Gly and tRNA Ile accompany changes in T-loop structure, suggesting impaired substrate binding to enzyme.

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tRNase Z Catalysis and Conserved Residues on the Carboxy Side of the His Cluster

Cited by 19 publications

References 28 publications

Protein factors in pre-mRNA 3′-end processing

Protein factors in pre-mRNA 3′-end processing

Structure of PhnP, a Phosphodiesterase of the Carbon-Phosphorus Lyase Pathway for Phosphonate Degradation

Pathogenesis-related mutations in the T-loops of human mitochondrial tRNAs affect 3′ end processing and tRNA structure

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