Liver arginase. III. Properties of highly purified arginase

Greenberg, David M.; Bagot, Albert E.; Roholt, Oliver A.

doi:10.1016/0003-9861(56)90143-6

Cited by 49 publications

(15 citation statements)

References 5 publications

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“…Parenthetically, we note that this complex does not contain Zn 2+ D or Zn 2+ E ions bound to the surface sites observed in the Zn 2+ 5 -human arginase I-ABH complex. This crystal structure shows that the inhibition 20-23 of arginase by Zn 2+ results from the coordination of H141 to Zn 2+ . This is consistent with mutagenesis studies of H141 in rat liver arginase demonstrating the catalytic importance of this residue.…”

Section: Resultsmentioning

confidence: 86%

Structure and Function of Non-Native Metal Clusters in Human Arginase I

2012

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Various binuclear metal ion clusters and complexes have been reconstituted in crystalline human arginase I by removing the Mn2+2-cluster of the wild-type enzyme with metal chelators and subsequently soaking the crystalline apoenzyme in buffer solutions containing NiCl2 or ZnCl2. X-ray crystal structures of these metal ion variants are correlated with catalytic activity measurements that reveal differences resulting from metal ion substitution. Additionally, treatment of crystalline Mn2+2-human arginase I with Zn2+ reveals for the first time the structural basis for inhibition by Zn2+, which forms a carboxylate-histidine-Zn2+ triad with H141 and E277. The imidazole side chain of H141 is known to be hyper-reactive and its chemical modification or mutagenesis is known to similarly compromise catalysis. The reactive substrate analogue 2(S)-amino-6-boronohexanoic acid (ABH) binds as a tetrahedral boronate anion to Mn2+2, Co2+2, Ni2+2, and Zn2+2 clusters in human arginase I, and it can be stabilized by a third inhibitory Zn2+ ion coordinated by H141. Since ABH binds as an analogue of the tetrahedral intermediate and its flanking transition states in catalysis, this implies that the various metallosubstituted enzymes are capable of some level of catalysis with an actual substrate. Accordingly, we establish the following trend for turnover number (kcat) and catalytic efficiency (kcat/KM): Mn2+ > Ni2+ ≈ Co2+ ≫ Zn2+. Therefore, Mn2+ is required for optimal catalysis by human arginase I.

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Section: Resultsmentioning

confidence: 86%

Structure and Function of Non-Native Metal Clusters in Human Arginase I

2012

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“…Mammalian arginase and most other arginases are not or only moderately sensitive to reducing agents (Greenberg et al, 1956; Mora et al, 1966; Soru, 1983), indicating that disulphide bonds are not important for their enzymatic activity. An interesting exception is arginase from H. pylori , which is strongly inhibited by DTT and 2-mercaptoethanol (2-ME) (McGee et al, 2004).…”

Section: Resultsmentioning

confidence: 99%

“…Strikingly, reducing agents strongly inhibited SmARG activity, while mammalian and many other arginases are not sensitive to the blockage of disulphide-bonds (Greenberg et al, 1956; Mora et al, 1966; Soru, 1983). On the contrary, a recent study showed that S -nitrosylation of cysteine residue 303 in HsARG-1 causes arginase activation (Santhanam et al, 2007).…”

Section: Discussionmentioning

confidence: 99%

Schistosoma mansoni arginase shares functional similarities with human orthologs but depends upon disulphide bridges for enzymatic activity

Fitzpatrick

Fuentes

Chalmers

et al. 2009

International Journal for Parasitology

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Schistosome helminths constitute a major health risk for the human population in many tropical areas. We demonstrate for the first time that several developmental stages of the human parasite Schistosoma mansoni express arginase, which is responsible for the hydrolysis of L-arginine to Lornithine and urea. Arginase activity by alternatively activated macrophages is an essential component of the mammalian host response in schistosomiasis. However, it has not been previously shown that the parasite also expresses arginase when it is in contact with the mammalian host. After cloning and sequencing the cDNA encoding the parasite enzyme, we found that many structural features of human arginase are well conserved in the parasite ortholog. Subsequently, we discovered that S. mansoni arginase shares many similar molecular, biochemical and functional properties with both human arginase isoforms. Nevertheless, our data also reveal striking differences between human and schistosome arginase. Particularly, we found evidence that schistosome arginase activity depends upon disulphide bonds by cysteines, in contrast to human arginase. In conclusion, we report that S. mansoni arginase is well adapted to the physiological conditions that exist in the human host.

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“…(92,93) have continued their studies of liver arginase and have obtained a preparation which is homogeneous both by electrophore sis and sedimentation, with a molecular weight of 138,000. The enzyme ex hibits a turnover number of 1.32 X 106 moles of arginine per mole of enzyme per min.…”

Section: Urea Synthesismentioning

confidence: 98%

Amino Acid and Protein Metabolism

Kamin¹,

Handler²

1957

Annu. Rev. Biochem.

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AMMONIAThe central metabolic position of ammonia has received renewed atten tion in recent years. To the list of known ammonia-producing reactions in mammals, summarized by Bessman (1), has been added the following: formylation of THF A2 from formiminoglutamate (2, 3) and, in microbial sources, L-alanine dehydrogenase (4); formylation from formimino glycine (S to 11); reductive deamination from glycine (12); and the degradation of glucosamine-6-phosphate (13). Since the fate of the nitrogen of numerous compounds is at present unknown, this list may be expected to expand an nually. Crystalline glutamic dehydrogenase isolated from corn leaves by Bulen (14) is DPN -specific, sensitive to sulfide reagents, and in general resembles the enzyme obtained from mammalian sources. Since the amino nitrogen of L-amino acids can be directed toward glutamate by transamina tion, it appears that glutamic dehydrogenase is the enzyme responsible for the major production of ammonia in hepatic metabolism in the steady state; it is not equally certain, however, that glutamic dehydrogenase universally occupies so central a role. Of various strains of B. subtilis which have been isolated, only those which possess glutamic dehydrogenase can use NH 3 as the sole nitrogen source (15). However, a mutant (5-) which can use am monia lacks glutamic dehydrogenase yet is capable of oxidizing glutamate (4). Fractionation of lysozyme-treated cells yielded a DPN-specific L-alanine 1 The survey of the literature pertaining to this review included journals received through Novemb er, 1956.2 The following abbreviations are used in this chapter: AICAR for 4-amino 5-imidazole carboxamide ribotide; ADP for adenosinediphosphate; AMP for adeno sinemonophosphate; ATP for adenosinetriphosphate; CoA for coenzyme Aj CSA for cysteine sulfinic acid; CTP for cytidinetriphosphate; DAP for diaminopimelic acid; DNA for deoxyribonuc leic acid; DNP for 2,4-dinitrophenol; DOPA for 3,4-dihydroxy phenylalanine; DPN for diphosphopyridine nucleotide; DPNH for diphosphopyridine nucleotide (reduced form); EDT A for ethylenediamine tetraacetic acid ; FAD for flavin adenine dinucleotide; FI G for formimino glycine; FGAR for formyl glycinamide ribotide; FMN for riboflavin phosphate; GAR for glycinamide ribotide; GDP for guanosinediphosphate; GMP for guanosinemonophosphate; GTP for guanosinetri phosphate; IDP for inosine diphosphate; IGP for imidazole glycerol phosphate; IMP for inosinemonophosphate; INH for isonicotinylhydrazide; ITP for inosinetriphos phate; PCMB for p-chloromercuribenzoate; Pi for inorganic phosphate; PBi for in organic pyrophosphate; PRPP for 5-phosphoribosylpyrophosphate; RNA for ribo nucleic acid; THF A for tetrahydrofolic acid; TPN for triphosphopyridine nucleotide; TPNH fortriphosphopyridine nucleotide (reduced form); Tris for trishydroxymethyl aminomethane; and UTP for uridinetriphosphate. 419Annu. Rev. Biochem. 1957.26:419-490. Downloaded from www.annualreviews.org Access provided by Texas Christian University on 02/03/15. For personal use only.Quick l...

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Liver arginase. III. Properties of highly purified arginase

Cited by 49 publications

References 5 publications

Structure and Function of Non-Native Metal Clusters in Human Arginase I

Structure and Function of Non-Native Metal Clusters in Human Arginase I

Schistosoma mansoni arginase shares functional similarities with human orthologs but depends upon disulphide bridges for enzymatic activity

Amino Acid and Protein Metabolism

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