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Literature summary for 3.1.4.37 extracted from

  • Myllykoski, M.; Raasakka, A.; Lehtimaeki, M.; Han, H.; Kursula, I.; Kursula, P.
    Crystallographic analysis of the reaction cycle of 2',3'-cyclic nucleotide 3'-phosphodiesterase, a unique member of the 2H phosphoesterase family (2013), J. Mol. Biol., 425, 4307-4322.
    View publication on PubMed
Search for more literature for 3.1.4.37

Crystallization (Commentary)

Crystallization (Comment) Organism
wild-type and mutant enzymes complexed with substrate 2',3'-cyclic AMP, product 2'-AMP, and phosphorothioate analogues, and H230S mutant complexed with the substrate 2',3'-cNADP+, X-ray diffraction structure determination and analysis at 1.9-2.3 A resolution Mus musculus

Protein Variants

Protein Variants Comment Organism
H230Q site-directed mutagenesis, the mutation of the active site residue highly reduces the enzyme activity compared to the wild-type enzyme Mus musculus
H230Q/H309Q site-directed mutagenesis, the mutation of the active site residue completely abolishes enzyme activity compared to the wild-type enzyme Mus musculus
H230S site-directed mutagenesis, the mutation of the active site residue highly reduces enzyme activity compared to the wild-type enzyme Mus musculus
H309Q site-directed mutagenesis, the mutation of the active site residue highly reduces enzyme activity compared to the wild-type enzyme Mus musculus
H309S site-directed mutagenesis, the mutation of the active site residue completely abolishes enzyme activity compared to the wild-type enzyme Mus musculus
V321A site-directed mutagenesis, Val321 stacks against the substrate adenine ring, the mutation does not affect kcat significantly but doubles Km, indicating a functional active site but slightly compromised substrate binding Mus musculus

KM Value [mM]

KM Value [mM] KM Value Maximum [mM] Substrate Comment Organism Structure
0.553
-
 2',3'-Cyclic AMP wild-type enzyme, pH and temperature not specified in the publication Mus musculus
1.045
-
 2',3'-Cyclic AMP mutant V321A, pH and temperature not specified in the publication Mus musculus
1.055
-
 2',3'-Cyclic AMP mutant H230Q, pH and temperature not specified in the publication Mus musculus
1.192
-
 2',3'-Cyclic AMP mutant H309S, pH and temperature not specified in the publication Mus musculus
1.305
-
 2',3'-Cyclic AMP mutant H230S, pH and temperature not specified in the publication Mus musculus

Natural Substrates/ Products (Substrates)

Natural Substrates Organism Comment (Nat. Sub.) Natural Products Comment (Nat. Pro.) Rev. Reac.
nucleoside 2',3'-cyclic phosphate + H2O Mus musculus
-
 nucleoside 2'-phosphate
-
 ?

Organism

Organism UniProt Comment Textmining
Mus musculus P16330
-
-

Reaction

Reaction Comment Organism Reaction ID
nucleoside 2',3'-cyclic phosphate + H2O = nucleoside 2'-phosphate during catalytic mechanism, a 2',3'-cyclic nucleotide is converted into a 2'-nucleotide through a nucleophilic attack carried out by an activated water molecule, dinucleotide binding mode, overview Mus musculus
a

Substrates and Products (Substrate)

Substrates Comment Substrates Organism Products Comment (Products) Rev. Reac.
2',3'-cNADP+ + H2O
-
 Mus musculus ?
-
 ?
2',3'-cyclic AMP + H2O substrate and product enzyme binding structures, overview Mus musculus 2'-AMP
-
 ?
adenosine 2,3-cyclic phosphorothioate + H2O the Sp epimer of 2',3'-cAMPS is a functional substrate for the enzyme, while the Rp epimer is not Mus musculus ?
-
 ?
nucleoside 2',3'-cyclic phosphate + H2O
-
 Mus musculus nucleoside 2'-phosphate
-
 ?
nucleoside 2',3'-cyclic phosphate + H2O dinucleotide binding mode, overview Mus musculus nucleoside 2'-phosphate
-
 ?

Subunits

Subunits Comment Organism
More the two domains of the enzyme form an elongated molecule, three-dimensional model of full-length enzyme, overveiw Mus musculus

Synonyms

Synonyms Comment Organism
2',3'-cyclic nucleotide 3'-phosphodiesterase
-
 Mus musculus
CNPase
-
 Mus musculus

Turnover Number [1/s]

Turnover Number Minimum [1/s] Turnover Number Maximum [1/s] Substrate Comment Organism Structure
14
-
 2',3'-Cyclic AMP mutant H230S, pH and temperature not specified in the publication Mus musculus
21
-
 2',3'-Cyclic AMP mutant H309S, pH and temperature not specified in the publication Mus musculus
24
-
 2',3'-Cyclic AMP mutant H230Q, pH and temperature not specified in the publication Mus musculus
732
-
 2',3'-Cyclic AMP mutant V321A, pH and temperature not specified in the publication Mus musculus
940
-
 2',3'-Cyclic AMP wild-type enzyme, pH and temperature not specified in the publication Mus musculus

General Information

General Information Comment Organism
evolution the enzyme is a unique member of the 2H phosphoesterase family. 2H phosphoesterases differ in their respective reaction mechanisms despite the conserved catalytic residues. The HxS/Tx motifs of the catalytic phosphodiesterase domain are conserved throughout species, domains structure comparison, overview. Conservation of ligand-binding residues Mus musculus
additional information the enzyme shows an open/close motion of the beta5-alpha7 loop linked to the reaction. The two domains of the enzyme form an elongated molecule. The active site includes the two HxTx motifs on beta strands beta2 and beta5, between which lie four water molecules, forming the bottom of the active site. The N-terminus of helix alpha7, which is unique for the enzyme in the 2H family, plays a role during the reaction indicating that 2H phosphoesterases differ in their respective reaction mechanisms despite the conserved catalytic residues Mus musculus

kcat/KM [mM/s]

kcat/KM Value [1/mMs-1] kcat/KM Value Maximum [1/mMs-1] Substrate Comment Organism Structure
10
-
 2',3'-Cyclic AMP mutant H230S, pH and temperature not specified in the publication Mus musculus
20
-
 2',3'-Cyclic AMP mutant H230Q, pH and temperature not specified in the publication Mus musculus
20
-
 2',3'-Cyclic AMP mutant H309S, pH and temperature not specified in the publication Mus musculus
700
-
 2',3'-Cyclic AMP mutant V321A, pH and temperature not specified in the publication Mus musculus
1700
-
 2',3'-Cyclic AMP wild-type enzyme, pH and temperature not specified in the publication Mus musculus