PROSITE documentation PDOC00135

Arginase family signature and profile




Description

Arginase family proteins are ureohydrolases with important roles in arginine/agmatine metabolism, the urea cycle, histidine degradation, and other pathways. The family includes arginase and evolutionary related [1] enzymes of about 300 amino acids that typically contain two manganese ions in the active site.

Some proteins that belong to the arginase family are listed below:

  • Arginase (EC 3.5.3.1), a ubiquitous enzyme which catalyzes the degradation of arginine to ornithine and urea [2]. Two isoenzymes are found in mammals. Arginase-1 catalyzes the final cytosolic step of the urea cycle in liver, but it is also found in non-hepatic tissues. Arginase-2 is a mitochondrial enzyme that functions in arginine homeostasis in nonhepatic tissues. Deficiency of arginase can lead to diseases related to the accumulation of arginine or ammonia.
  • Agmatinase (EC 3.5.3.11) (agmatine ureohydrolase), a prokaryotic enzyme (gene speB) that catalyzes the hydrolysis of agmatine into putrescine and urea.
  • Formiminoglutamase (EC 3.5.3.8) (formiminoglutamate hydrolase), a prokaryotic enzyme (gene hutG) that hydrolyzes N-formimino-glutamate into glutamate and formamide.
  • Proclavaminate amidinohydrolase (EC 3.5.3.22) from Streptomyces clavuligerus (gene pah), an enzyme involved in antibiotic clavulanic acid biosynthesis.
  • Guanidinobutyrase (EC 3.5.3.7) from Arthrobacter sp. (gene gbh), an enzyme that hydrolyzes guanidinobutanoate into aminobutanoate and urea and that requires one zinc ion instead of manganese.
  • Hypothetical proteins from methanogenic archaebacteria.

Known 3-D structures of such enzymes show trimeric or hexameric structures [3,4,5,6]. Each monomer forms a conserved α/β fold with a central parallel β-sheet flanked on both sides by several α-helices (see <PDB:1RLA; B>). Three conserved regions that contain charged residues which are involved in the binding of the two manganese ions in the active site are located in loop segments of the central β-sheet [3,4,5,6]. We have used one of these regions for a signature pattern and we have also developed a profile that covers the entire arginase structure.

Expert(s) to contact by email:

Ouzounis C.

Last update:

November 2008 / Text revised; profile added; patterns deleted.

Technical section

PROSITE methods (with tools and information) covered by this documentation:

ARGINASE_2, PS51409; Arginase family profile  (MATRIX)

ARGINASE_1, PS01053; Arginase family signature  (PATTERN)


References

1AuthorsOuzounis C.A., Kyrpides N.C.
TitleOn the evolution of arginases and related enzymes.
SourceJ. Mol. Evol. 39:101-104(1994).
PubMed ID8064866

2AuthorsJenkinson C.P., Grody W.W., Cederbaum S.D.
TitleComparative properties of arginases.
SourceComp. Biochem. Physiol. 114B:107-132(1996).
PubMed ID8759304

3AuthorsKanyo Z.F., Scolnick L.R., Ash D.E., Christianson D.W.
TitleStructure of a unique binuclear manganese cluster in arginase.
SourceNature 383:554-557(1996).
PubMed ID8849731

4AuthorsElkins J.M., Clifton I.J., Hernandez H., Doan L.X., Robinson C.V., Schofield C.J., Hewitson K.S.
TitleOligomeric structure of proclavaminic acid amidino hydrolase: evolution of a hydrolytic enzyme in clavulanic acid biosynthesis.
SourceBiochem. J. 366:423-434(2002).
PubMed ID12020346
DOI10.1042/BJ20020125

5AuthorsAhn H.J., Kim K.H., Lee J., Ha J.Y., Lee H.H., Kim D., Yoon H.J., Kwon A.R., Suh S.W.
TitleCrystal structure of agmatinase reveals structural conservation and inhibition mechanism of the ureohydrolase superfamily.
SourceJ. Biol. Chem. 279:50505-50513(2004).
PubMed ID15355972
DOI10.1074/jbc.M409246200

6AuthorsDowling D.P., Di Costanzo L., Gennadios H.A., Christianson D.W.
TitleEvolution of the arginase fold and functional diversity.
SourceCell. Mol. Life Sci. 65:2039-2055(2008).
PubMed ID18360740
DOI10.1007/s00018-008-7554-z



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