Literature summary for 4.6.1.19 extracted from

Garvie, C.W.; Vasanthavada, K.; Xiang, Q.
Mechanistic insights into RNase L through use of an MDMX-derived multi-functional protein domain (2013), Biochim. Biophys. Acta, 1834, 1562-1571.

Activating Compound

Activating Compound	Comment	Organism	Structure
2'-5'-oligoadenylate	short polyadenylate molecules that are connected by unique 2'-5' linkages, collectively referred to as 2-5A. 2-5A induces dimerization via the ANK domain and this dimerization correlates with activation of ribonuclease activity	Homo sapiens

Cloned(Commentary)

Cloned (Comment)	Organism
recombinant expression of His6-tagged enzyme with or without TEV cleavage site inserted after residue 333 and the amino acid sequence of ZMP comprised residues 15 to 129 of zebrafish MDMX with two mutations L46V and V95L, in Escherichia coli strain BL21(DE3) or in Spodoptera frugiperda Sf9 insect cells. The zebrafish sequence ZMP is a unique dimerization inducing domain and represents a tool protein for solving crystal structures of inhibitors binding to the p53-interacting domain of MDMX	Homo sapiens

Cloned (Comment)

Organism

recombinant expression of His6-tagged enzyme with or without TEV cleavage site inserted after residue 333 and the amino acid sequence of ZMP comprised residues 15 to 129 of zebrafish MDMX with two mutations L46V and V95L, in Escherichia coli strain BL21(DE3) or in Spodoptera frugiperda Sf9 insect cells. The zebrafish sequence ZMP is a unique dimerization inducing domain and represents a tool protein for solving crystal structures of inhibitors binding to the p53-interacting domain of MDMX

Homo sapiens

Protein Variants

Protein Variants	Comment	Organism
additional information	generation of the truncated enzyme mutant RNase L(1-333) by insering a TEV cleavage site into the recombinant enzyme and cleaving it into two proteins, truncated enzyme comprising residues 432-741 shows proteolytic stability and no change in oligomeric state in the absence and presence ofMg2+ and ATP	Homo sapiens

General Stability

General Stability	Organism
Mg2+ and ATP or ADP protect the enzyme from proteolytic cleavage	Homo sapiens

Metals/Ions

Metals/Ions	Comment	Organism	Structure
additional information	Mg2+ and ATP or ADP protect the enzyme from proteolytic cleavage	Homo sapiens

Molecular Weight [Da]

Molecular Weight [Da]	Molecular Weight Maximum [Da]	Comment	Organism
35000	-	recombinant truncated enzyme RNase L(1-306), gel filtration	Homo sapiens
37000	-	recombinant truncated enzyme RNase L(1-333), gel filtration	Homo sapiens
62100	-	recombinant truncated enzyme RNase L(1-333) with bound 2'-5'-oligoadenylate, gel filtration	Homo sapiens

Natural Substrates/ Products (Substrates)

Natural Substrates	Organism	Comment (Nat. Sub.)	Natural Products	Comment (Nat. Pro.)	Rev.	Reac.
additional information	Homo sapiens	the enzyme cleaves single-stranded RNA molecules	?	-	?

Organism

Organism	UniProt	Comment	Textmining
Homo sapiens	-	-	-

Purification (Commentary)

Purification (Comment)	Organism
recombinant His6-tagged enzyme variants from Escherichia coli strain BL21(DE3) or Spodoptera frugiperda Sf9 insect cells by ultracentrifugation, nickel affinity chromatography and gel filtration, dialysis, anion exchange chromatography, clevage by TEV protease and again nickel affinity chromatography, gel filtration and	Homo sapiens

Substrates and Products (Substrate)

Substrates	Comment Substrates	Organism	Products	Comment (Products)	Rev.	Reac.
additional information	the enzyme cleaves single-stranded RNA molecules	Homo sapiens	?	-	?

Subunits

Subunits	Comment	Organism
More	dimerization of recombinant, ZMP-domain-containing enzyme can be induced by a small organic molecule, RO-2443. But dimerization of RNase L induced by RO-2443 is not sufficient for activation of ribonuclease activity but requires a conformational rearrangement induced by 2'-5'-oligoadenylate that is distinct from the dimer induced by RO-2443	Homo sapiens

Synonyms

Synonyms	Comment	Organism
RNase L	-	Homo sapiens

General Information

General Information	Comment	Organism
additional information	the kinase-like region is required for the ribonuclease activity of the enzyme	Homo sapiens
physiological function	the ribonuclease RNase L is activated by the binding to 2'-5'-oligoadenylates and it proceeds to cleave single-stranded RNA molecules, ultimately leading to apoptosis of the virally infected cell	Homo sapiens