Purification and Characterization of Hepatic Inorganic Pyrophosphatase Hydrolyzing Imidodiphosphate

Hiraishi, Hiroyuki; Ohmagari, Takao; Otsuka, Yasufumi; Yokoi, Fumiaki; Kumon, Akira

doi:10.1006/abbi.1997.9935

Cited by 16 publications

(14 citation statements)

References 21 publications

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“…171 The Cut-1 subfamily (after the Cut-1 protein from Neurospora) is encoded in a predicted operon in α-proteobacteria with the bifunctional riboflavin kinase/FAD synthetase protein (RibF) and an adenyltransferase that catalyzes the formation of FAD, and might function in cofactor biosynthesis. Except for the phosphohistidine/phospholysine phosphatase 172,173 subfamily (Table 1), all the other members of the NagD family contain a highly conserved aspartate in the C2 Cap (D149 in 1VJR), which points towards the active site and likely acts as a substrate recognition feature.…”

Section: C2 Caps: the Nagd Familymentioning

confidence: 99%

Evolutionary Genomics of the HAD Superfamily: Understanding the Structural Adaptations and Catalytic Diversity in a Superfamily of Phosphoesterases and Allied Enzymes

Burroughs¹,

Allen²,

Dunaway‐Mariano³

et al. 2006

Journal of Molecular Biology

387

520

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The HAD (haloacid dehalogenase) superfamily includes phosphoesterases, ATPases, phosphonatases, dehalogenases, and sugar phosphomutases acting on a remarkably diverse set of substrates. The availability of numerous crystal structures of representatives belonging to diverse branches of the HAD superfamily provides us with a unique opportunity to reconstruct their evolutionary history and uncover the principal determinants that led to their diversification of structure and function. To this end we present a comprehensive analysis of the HAD superfamily that identifies their unique structural features and provides a detailed classification of the entire superfamily. We show that at the highest level the HAD superfamily is unified with several other superfamilies, namely the DHH, receiver (CheY-like), von Willebrand A, TOPRIM, classical histone deacetylases and PIN/FLAP nuclease domains, all of which contain a specific form of the Rossmannoid fold. These Rossmannoid folds are distinguished from others by the presence of equivalently placed acidic catalytic residues, including one at the end of the first core β-strand of the central sheet. The HAD domain is distinguished from these related Rossmannoid folds by two key structural signatures, a "squiggle" (a single helical turn) and a "flap" (a beta hairpin motif) located immediately downstream of the first β-strand of their core Rossmanoid fold. The squiggle and the flap motifs are predicted to provide the necessary mobility to these enzymes for them to alternate between the "open" and "closed" conformations. In addition, most members of the HAD superfamily contains inserts, termed caps, occurring at either of two positions in the core Rossmannoid fold. We show that the cap modules have been independently inserted into these two stereotypic positions on multiple occasions in evolution and display extensive evolutionary diversification independent of the core catalytic domain. The first group of caps, the C1 caps, is directly inserted into the flap motif and regulates access of reactants to the active site. The second group, the C2 caps, forms a roof over the active site, and access to their internal cavities might be in part regulated by the movement of the flap. The diversification of the cap module was a major factor in the exploration of a vast substrate space in the course of the evolution of this superfamily. We show that the HAD superfamily contains 33 major families distributed across the three superkingdoms of life. Analysis of the phyletic patterns suggests that at least five distinct HAD proteins are traceable to the last universal common ancestor (LUCA) of all extant organisms. While these prototypes diverged prior to the emergence Abbreviations used: HAD, haloacid dehalogenase; PNKP, polynucleotide kinase phosphatase; KDO 8-P, deoxy-Dmannose-octulosonate 8-phosphate; CTD, carboxyl-terminal domain; PNKP, polynucleotide kinase phosphatase; LUCA, last universal common ancestor.E-mail address of the corresponding author: aravind@ncbi.nlm.nih.gov of the LUCA, t...

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Section: C2 Caps: the Nagd Familymentioning

confidence: 99%

Evolutionary Genomics of the HAD Superfamily: Understanding the Structural Adaptations and Catalytic Diversity in a Superfamily of Phosphoesterases and Allied Enzymes

Burroughs¹,

Allen²,

Dunaway‐Mariano³

et al. 2006

Journal of Molecular Biology

387

520

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“…Phosphoramidate hydrolase and phosphatase assay to evaluate the LHPP substrate scope To minimize phosphoramidate bond hydrolysis even without enzyme being present, fast sample preparation, distinct pH adjustment and storage at low temperature were crucial. Whereas previous studies to monitor LHPP activity relied on detection of released inorganic phosphate (P i ) using Rosenberg's reagent 9 or malachite green, 8,10 we considered both methods as too time consuming to meet the stability prole of pLys peptides. State of the art real-time detection of released P i can be conducted conveniently in cuvette-or microplate-based experiments and we desired a similar set up to conduct kinetic experiments.…”

Section: Resultsmentioning

confidence: 99%

“…Subsequently the enzymatic hydrolase activity was shown, rst for pyrophosphate (PP i ) and imidodiphosphate (PNP), later for the single amino acids 3-phospho-lysine (pLys) and 3-phospho-histidine (3-pHis). 8,9 While researchers could observe slightly higher activity for PNP compared to PP i (0.44 mmol min À1 mg À1 and 0.11 mmol min À1 mg À1 released phosphate at pH 8.2 in the presence of 1 mM MgCl 2 ) as well as for pLys compared to pHis (1.22 mmol min À1 mg À1 and 1.09 mmol min À1 mg À1 released phosphate at pH 8.2 in the presence of 1 mM MgCl 2 ), no structural information about the binding event of pLys or pHis residues to LHPP is currently known. Furthermore, besides small molecules, no endogenous pLyscontaining peptide or protein substrates for LHPP were reported to date and thus, no standardized value that describes catalytic potency has been established.…”

Section: Introductionmentioning

confidence: 99%

Combining free energy calculations with tailored enzyme activity assays to elucidate substrate binding of a phospho-lysine phosphatase

et al. 2020

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“…LHPP LHPP,a56 kDa enzyme first isolated from bovine liver in 1997 by Hiraishi et al,w as initially characterizeda sa ni norganic pyrophosphatase. [58] Free t-pHis and pLys amino acids were identified as additional in vitro substrates, but no peptide or protein substrates were tested. [59] Later,t he same group successfully cloned human LHPP to show that the recombinant enzyme had the same activity.…”

Section: Phpt1mentioning

confidence: 99%

Recent Updates on Protein N‐Phosphoramidate Hydrolases

2018

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In contrast to well‐recognized protein phosphorylation on the side‐chain oxygen of Ser, Thr, or Tyr residues, analogous phosphoramidation of the nitrogen of His, Lys, and Arg side chains remains much less investigated, mainly due to the instability of post‐translational modifications and technical difficulties involved in their analysis. For example, reports on the enzyme activities responsible for the formation and hydrolysis of these phosphoramidates date back to as early as the 1950s, but some of these enzymes have only recently been identified and functionally characterized; this has been aided by the development of novel research tools. In this review, we summarize current knowledge of the enzymes that hydrolyze protein N‐phosphoramidates, in terms of their structure, activities, and biological functions, as well as the chemical tools used to investigate them.

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Purification and Characterization of Hepatic Inorganic Pyrophosphatase Hydrolyzing Imidodiphosphate

Cited by 16 publications

References 21 publications

Evolutionary Genomics of the HAD Superfamily: Understanding the Structural Adaptations and Catalytic Diversity in a Superfamily of Phosphoesterases and Allied Enzymes

Evolutionary Genomics of the HAD Superfamily: Understanding the Structural Adaptations and Catalytic Diversity in a Superfamily of Phosphoesterases and Allied Enzymes

Combining free energy calculations with tailored enzyme activity assays to elucidate substrate binding of a phospho-lysine phosphatase

Recent Updates on Protein N‐Phosphoramidate Hydrolases

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