Literature summary for 2.7.7.72 extracted from

M�rl, M.; Betat, H.; Rammelt, C.
TRNA nucleotidyltransferases: ancient catalysts with an unusual mechanism of polymerization (2010), Cell. Mol. Life Sci., 67, 1447-1463.

Activating Compound

Activating Compound	Comment	Organism
protein Hfq	the multifunctional protein Hfq, originally discovered as a host factor for phage Qb, can stimulate the CCA-adding activity, Hfq facilitates the release of the reaction product, after CCA addition has taken place	Thermus thermophilus
protein Hfq	the multifunctional protein Hfq, originally discovered as a host factor for phage Qb, can stimulate the CCA-adding activity, Hfq facilitates the release of the reaction product, after CCA addition has taken place	Escherichia coli
protein Hfq	the multifunctional protein Hfq, originally discovered as a host factor for phage Qb, can stimulate the CCA-adding activity, Hfq facilitates the release of the reaction product, after CCA addition has taken place	Homo sapiens
protein Hfq	the multifunctional protein Hfq, originally discovered as a host factor for phage Qb, can stimulate the CCA-adding activity, Hfq facilitates the release of the reaction product, after CCA addition has taken place	Geobacillus stearothermophilus

Crystallization (Commentary)

Crystallization (Comment)	Organism
crystal structure analysis	Escherichia coli
crystal structure analysis	Archaeoglobus fulgidus
crystal structure analysis	Thermotoga maritima

Metals/Ions

Metals/Ions	Comment	Organism	Structure
Mg2+	two metal ions are bound to the two catalytically important carboxylates. The first metal ion deprotonates the 3'-OH group of the tRNA primer and activates the resulting 3'-O for an attack at the a-phosphate of the incoming nucleotide. The second metal ion stabilizes the triphosphate moiety of the NTP and facilitates the leaving of the pyrophosphate group, overview	Archaeoglobus fulgidus

Natural Substrates/ Products (Substrates)

Natural Substrates	Organism	Comment (Nat. Sub.)	Natural Products	Comment (Nat. Pro.)	Rev.
additional information	Thermus thermophilus	CCA-adding enzymes recognize tRNA and tRNA-like structures as substrates, select and discriminate the correct nucleotides CTP and ATP against UTP and GTP, and, after incorporation of two C residues, the nucleotide specificity has to switch towards ATP without the help of a nucleic acid template. The enzymes have to stop polymerization exactly after three positions and recognize partial CCA-ends and add only the missing residues for completion, instead of stubbornly adding CCA-ends to their substrates, overview	?	-	?
additional information	Escherichia coli	CCA-adding enzymes recognize tRNA and tRNA-like structures as substrates, select and discriminate the correct nucleotides CTP and ATP against UTP and GTP, and, after incorporation of two C residues, the nucleotide specificity has to switch towards ATP without the help of a nucleic acid template. The enzymes have to stop polymerization exactly after three positions and recognize partial CCA-ends and add only the missing residues for completion, instead of stubbornly adding CCA-ends to their substrates, overview	?	-	?
additional information	Homo sapiens	CCA-adding enzymes recognize tRNA and tRNA-like structures as substrates, select and discriminate the correct nucleotides CTP and ATP against UTP and GTP, and, after incorporation of two C residues, the nucleotide specificity has to switch towards ATP without the help of a nucleic acid template. The enzymes have to stop polymerization exactly after three positions and recognize partial CCA-ends and add only the missing residues for completion, instead of stubbornly adding CCA-ends to their substrates, overview	?	-	?
additional information	Geobacillus stearothermophilus	CCA-adding enzymes recognize tRNA and tRNA-like structures as substrates, select and discriminate the correct nucleotides CTP and ATP against UTP and GTP, and, after incorporation of two C residues, the nucleotide specificity has to switch towards ATP without the help of a nucleic acid template. The enzymes have to stop polymerization exactly after three positions and recognize partial CCA-ends and add only the missing residues for completion, instead of stubbornly adding CCA-ends to their substrates, overview	?	-	?
additional information	Saccharolobus shibatae	CCA-adding enzymes recognize tRNA and tRNA-like structures as substrates, select and discriminate the correct nucleotides CTP and ATP against UTP and GTP, and, after incorporation of two C residues, the nucleotide specificity has to switch towards ATP without the help of a nucleic acid template. The enzymes have to stop polymerization exactly after three positions and recognize partial CCA-ends and add only the missing residues for completion, instead of stubbornly adding CCA-ends to their substrates, overview	?	-	?
additional information	Archaeoglobus fulgidus	CCA-adding enzymes recognize tRNA and tRNA-like structures as substrates, select and discriminate the correct nucleotides CTP and ATP against UTP and GTP, and, after incorporation of two C residues, the nucleotide specificity has to switch towards ATP without the help of a nucleic acid template. The enzymes have to stop polymerization exactly after three positions and recognize partial CCA-ends and add only the missing residues for completion, instead of stubbornly adding CCA-ends to their substrates, overview	?	-	?
additional information	Thermotoga maritima	CCA-adding enzymes recognize tRNA and tRNA-like structures as substrates, select and discriminate the correct nucleotides CTP and ATP against UTP and GTP, and, after incorporation of two C residues, the nucleotide specificity has to switch towards ATP without the help of a nucleic acid template. The enzymes have to stop polymerization exactly after three positions and recognize partial CCA-ends and add only the missing residues for completion, instead of stubbornly adding CCA-ends to their substrates, overview	?	-	?

Organism

Organism	UniProt	Comment	Textmining
Archaeoglobus fulgidus	-	-	-
Escherichia coli	-	-	-
Geobacillus stearothermophilus	-	-	-
Homo sapiens	-	-	-
Saccharolobus shibatae	-	-	-
Thermotoga maritima	-	-	-
Thermus thermophilus	-	-	-

Reaction

Reaction	Comment	Organism	Reaction ID
a tRNA precursor + 2 CTP + ATP = a tRNA with a 3' CCA end + 3 diphosphate	catalytic core and reaction mechanism of class I CCA-adding enzymes, overview	Saccharolobus shibatae	a
a tRNA precursor + 2 CTP + ATP = a tRNA with a 3' CCA end + 3 diphosphate	catalytic core and reaction mechanism of class I CCA-adding enzymes, overview	Archaeoglobus fulgidus	a
a tRNA precursor + 2 CTP + ATP = a tRNA with a 3' CCA end + 3 diphosphate	catalytic core and reaction mechanism of class II CCA-adding enzymes, overview	Thermus thermophilus	a
a tRNA precursor + 2 CTP + ATP = a tRNA with a 3' CCA end + 3 diphosphate	catalytic core and reaction mechanism of class II CCA-adding enzymes, overview	Homo sapiens	a
a tRNA precursor + 2 CTP + ATP = a tRNA with a 3' CCA end + 3 diphosphate	catalytic core and reaction mechanism of class II CCA-adding enzymes, overview	Geobacillus stearothermophilus	a
a tRNA precursor + 2 CTP + ATP = a tRNA with a 3' CCA end + 3 diphosphate	catalytic core and reaction mechanism of class II CCA-adding enzymes, overview	Thermotoga maritima	a

Substrates and Products (Substrate)

Substrates	Comment Substrates	Organism	Products	Comment (Products)	Rev.
additional information	CCA-adding enzymes recognize tRNA and tRNA-like structures as substrates, select and discriminate the correct nucleotides CTP and ATP against UTP and GTP, and, after incorporation of two C residues, the nucleotide specificity has to switch towards ATP without the help of a nucleic acid template. The enzymes have to stop polymerization exactly after three positions and recognize partial CCA-ends and add only the missing residues for completion, instead of stubbornly adding CCA-ends to their substrates, overview	Thermus thermophilus	?	-	?
additional information	CCA-adding enzymes recognize tRNA and tRNA-like structures as substrates, select and discriminate the correct nucleotides CTP and ATP against UTP and GTP, and, after incorporation of two C residues, the nucleotide specificity has to switch towards ATP without the help of a nucleic acid template. The enzymes have to stop polymerization exactly after three positions and recognize partial CCA-ends and add only the missing residues for completion, instead of stubbornly adding CCA-ends to their substrates, overview	Escherichia coli	?	-	?
additional information	CCA-adding enzymes recognize tRNA and tRNA-like structures as substrates, select and discriminate the correct nucleotides CTP and ATP against UTP and GTP, and, after incorporation of two C residues, the nucleotide specificity has to switch towards ATP without the help of a nucleic acid template. The enzymes have to stop polymerization exactly after three positions and recognize partial CCA-ends and add only the missing residues for completion, instead of stubbornly adding CCA-ends to their substrates, overview	Homo sapiens	?	-	?
additional information	CCA-adding enzymes recognize tRNA and tRNA-like structures as substrates, select and discriminate the correct nucleotides CTP and ATP against UTP and GTP, and, after incorporation of two C residues, the nucleotide specificity has to switch towards ATP without the help of a nucleic acid template. The enzymes have to stop polymerization exactly after three positions and recognize partial CCA-ends and add only the missing residues for completion, instead of stubbornly adding CCA-ends to their substrates, overview	Geobacillus stearothermophilus	?	-	?
additional information	CCA-adding enzymes recognize tRNA and tRNA-like structures as substrates, select and discriminate the correct nucleotides CTP and ATP against UTP and GTP, and, after incorporation of two C residues, the nucleotide specificity has to switch towards ATP without the help of a nucleic acid template. The enzymes have to stop polymerization exactly after three positions and recognize partial CCA-ends and add only the missing residues for completion, instead of stubbornly adding CCA-ends to their substrates, overview	Saccharolobus shibatae	?	-	?
additional information	CCA-adding enzymes recognize tRNA and tRNA-like structures as substrates, select and discriminate the correct nucleotides CTP and ATP against UTP and GTP, and, after incorporation of two C residues, the nucleotide specificity has to switch towards ATP without the help of a nucleic acid template. The enzymes have to stop polymerization exactly after three positions and recognize partial CCA-ends and add only the missing residues for completion, instead of stubbornly adding CCA-ends to their substrates, overview	Archaeoglobus fulgidus	?	-	?
additional information	CCA-adding enzymes recognize tRNA and tRNA-like structures as substrates, select and discriminate the correct nucleotides CTP and ATP against UTP and GTP, and, after incorporation of two C residues, the nucleotide specificity has to switch towards ATP without the help of a nucleic acid template. The enzymes have to stop polymerization exactly after three positions and recognize partial CCA-ends and add only the missing residues for completion, instead of stubbornly adding CCA-ends to their substrates, overview	Thermotoga maritima	?	-	?

Synonyms

Synonyms	Comment	Organism
CCA-adding enzyme	-	Thermus thermophilus
CCA-adding enzyme	-	Escherichia coli
CCA-adding enzyme	-	Homo sapiens
CCA-adding enzyme	-	Geobacillus stearothermophilus
CCA-adding enzyme	-	Saccharolobus shibatae
CCA-adding enzyme	-	Archaeoglobus fulgidus
CCA-adding enzyme	-	Thermotoga maritima
class I CCA-adding enzyme	-	Saccharolobus shibatae
class I CCA-adding enzyme	-	Archaeoglobus fulgidus
class II CCA-adding enzyme	-	Thermus thermophilus
class II CCA-adding enzyme	-	Homo sapiens
class II CCA-adding enzyme	-	Geobacillus stearothermophilus
class II CCA-adding enzyme	-	Thermotoga maritima

General Information

General Information	Comment	Organism
evolution	a class I CCA-adding enzyme. CCA-adding enzymes are essential RNA polymerases that emerged twice in evolution leading to different structural characteristics and unusual mechanistic solutions for an error-free and sequence-specific CCA polymerization reaction. The catalytic cleft is formed by the head, neck, and body domains. Evolution of class I and class II CCA-adding enzymes as well as poly(A) polymerases, overview	Saccharolobus shibatae
evolution	a class I CCA-adding enzyme. CCA-adding enzymes are essential RNA polymerases that emerged twice in evolution leading to different structural characteristics and unusual mechanistic solutions for an error-free and sequence-specific CCA polymerization reaction. The catalytic cleft is formed by the head, neck, and body domains. Evolution of class I and class II CCA-adding enzymes as well as poly(A) polymerases, overview	Archaeoglobus fulgidus
evolution	a class II CCA-adding enzyme. Compared to class I, class II CCA-adding enzymes show a much higher evolutionary conservation of individual catalytic core motifs. Evolution of class I and class II CCA-adding enzymes as well as poly(A) polymerases, overview	Thermus thermophilus
evolution	a class II CCA-adding enzyme. Compared to class I, class II CCA-adding enzymes show a much higher evolutionary conservation of individual catalytic core motifs. Evolution of class I and class II CCA-adding enzymes as well as poly(A) polymerases, overview	Homo sapiens
evolution	a class II CCA-adding enzyme. Compared to class I, class II CCA-adding enzymes show a much higher evolutionary conservation of individual catalytic core motifs. Evolution of class I and class II CCA-adding enzymes as well as poly(A) polymerases, overview	Geobacillus stearothermophilus
evolution	a class II CCA-adding enzyme. Compared to class I, class II CCA-adding enzymes show a much higher evolutionary conservation of individual catalytic core motifs. The templating motif carries the sequence DDxxR, a slight deviation from the usual EDxxR motif. Evolution of class I and class II CCA-adding enzymes as well as poly(A) polymerases, overview	Thermotoga maritima
evolution	CCA-adding enzymes are essential RNA polymerases that emerged twice in evolution leading to different structural characteristics and unusual mechanistic solutions for an error-free and sequence-specific CCA polymerization reaction. Evolution of class I and class II CCA-adding enzymes as well as poly(A) polymerases, overview	Escherichia coli
malfunction	mutations around the active site of the Sulfolobus shibatae enzyme interfere with CCA-addition, but have only a minor affect on tRNA binding	Thermus thermophilus
malfunction	mutations around the active site of the Sulfolobus shibatae enzyme interfere with CCA-addition, but have only a minor affect on tRNA binding	Homo sapiens
malfunction	mutations around the active site of the Sulfolobus shibatae enzyme interfere with CCA-addition, but have only a minor affect on tRNA binding	Geobacillus stearothermophilus
malfunction	mutations around the active site of the Sulfolobus shibatae enzyme interfere with CCA-addition, but have only a minor affect on tRNA binding	Saccharolobus shibatae
malfunction	mutations around the active site of the Sulfolobus shibatae enzyme interfere with CCA-addition, but have only a minor affect on tRNA binding	Thermotoga maritima
malfunction	the enzyme knockout phenotype is a dramatic growth impairment, indicating the repair function of the CCA-adding enzyme on defective tRNAs lacking CCA ends due to hydrolytic damage	Escherichia coli
additional information	structure-function relationship, overview	Escherichia coli
additional information	structure-function relationship, overview	Saccharolobus shibatae
additional information	structure-function relationship, overview. The active site is located in the N-terminal part of the enzyme and consists of five elements that are involved in metal ion binding, catalysis, ribose recognition, nucleotide selection, and templating. Motif A is located in the head domain and includes the general signature motif of all nucleotidyltransferases with the two metal-binding carboxylates DxD that are involved in catalysis and binding of the triphosphate moiety of the incoming nucleotides. The head domain carries motif B, where highly conserved residues play a critical role in discriminating between NTPs and dNTPs. The neck domain contains motif D, a single nucleotide-binding pocket that is specific for binding of CTP and ATP. Head and neck domain form a cleft that binds the incoming nucleotide as well as the 3'-end of the tRNA primer. The body and tail domains at the enzyme's C-terminus recognize the top-half region of the tRNA primer. The CCA-enzyme does not move along the tRNA during synthesis but remains at a fixed position	Thermus thermophilus
additional information	structure-function relationship, overview. The active site is located in the N-terminal part of the enzyme and consists of five elements that are involved in metal ion binding, catalysis, ribose recognition, nucleotide selection, and templating. Motif A is located in the head domain and includes the general signature motif of all nucleotidyltransferases with the two metal-binding carboxylates DxD that are involved in catalysis and binding of the triphosphate moiety of the incoming nucleotides. The head domain carries motif B, where highly conserved residues play a critical role in discriminating between NTPs and dNTPs. The neck domain contains motif D, a single nucleotide-binding pocket that is specific for binding of CTP and ATP. Head and neck domain form a cleft that binds the incoming nucleotide as well as the 3'-end of the tRNA primer. The body and tail domains at the enzyme's C-terminus recognize the top-half region of the tRNA primer. The CCA-enzyme does not move along the tRNA during synthesis but remains at a fixed position	Homo sapiens
additional information	structure-function relationship, overview. The active site is located in the N-terminal part of the enzyme and consists of five elements that are involved in metal ion binding, catalysis, ribose recognition, nucleotide selection, and templating. Motif A is located in the head domain and includes the general signature motif of all nucleotidyltransferases with the two metal-binding carboxylates DxD that are involved in catalysis and binding of the triphosphate moiety of the incoming nucleotides. The head domain carries motif B, where highly conserved residues play a critical role in discriminating between NTPs and dNTPs. The neck domain contains motif D, a single nucleotide-binding pocket that is specific for binding of CTP and ATP. Head and neck domain form a cleft that binds the incoming nucleotide as well as the 3'-end of the tRNA primer. The body and tail domains at the enzyme's C-terminus recognize the top-half region of the tRNA primer. The CCA-enzyme does not move along the tRNA during synthesis but remains at a fixed position	Geobacillus stearothermophilus
additional information	structure-function relationship, overview. The active site is located in the N-terminal part of the enzyme and consists of five elements that are involved in metal ion binding, catalysis, ribose recognition, nucleotide selection, and templating. Motif A is located in the head domain and includes the general signature motif of all nucleotidyltransferases with the two metal-binding carboxylates DxD that are involved in catalysis and binding of the triphosphate moiety of the incoming nucleotides. The head domain carries motif B, where highly conserved residues play a critical role in discriminating between NTPs and dNTPs. The neck domain contains motif D, a single nucleotide-binding pocket that is specific for binding of CTP and ATP. Head and neck domain form a cleft that binds the incoming nucleotide as well as the 3'-end of the tRNA primer. The body and tail domains at the enzyme's C-terminus recognize the top-half region of the tRNA primer. The CCA-enzyme does not move along the tRNA during synthesis but remains at a fixed position	Thermotoga maritima
additional information	structure-function relationship, overview. The enzyme binds the tRNA top half in the correct orientation for CCA-addition in a cleft, the tRNA acceptor stem interacts with a highly conserved long alpha-helical element in an almost parallel orientation. In the position of nucleotide addition, the 3'-end is bound to the active site located in the enzyme's head domain, while the T loop of the tRNA contacts the tail domain. The bound tRNA substrate remains fixed at its binding site in the enzyme during the complete nucleotide incorporation process	Archaeoglobus fulgidus
physiological function	CCA-adding enzymes represent vital components of the cell's tRNA maturation and maintenance system. The CCA end, added to the tRNA by the CCA tRNA nucleotidyltransferase, is the site of aminoacylation, and aminoacyl tRNA synthetases fuse the individual amino acids to the ribose moiety of the terminal A residue. Second, the CCA terminus is required for the correct positioning of the aminoacyl-tRNA in the ribosome's A- and P-site in order to guarantee an efficient peptidyl transfer reaction. The CCA-adding enzyme represents an essential activity in the majority of organisms	Archaeoglobus fulgidus
physiological function	CCA-adding enzymes represent vital components of the cell's tRNA maturation and maintenance system. The CCA end, added to the tRNA by the CCA tRNA nucleotidyltransferase, is the site of aminoacylation, and aminoacyl tRNA synthetases fuse the individual amino acids to the ribose moiety of the terminal A residue. Second, the CCA terminus is required for the correct positioning of the aminoacyl-tRNA in the ribosome's A- and P-site in order to guarantee an efficient peptidyl transfer reaction. The CCA-adding enzyme represents an essential activity in the majority of organisms, but in Escherichia coli, on the other hand, where CCA ends are encoded, this enzyme is dispensable, and a corresponding gene knockout is not lethal, but the repair function of the CCA-adding enzyme on defective tRNAs lacking CCA ends due to hydrolytic damage is required	Escherichia coli
physiological function	CCA-adding enzymes represent vital components of the cell's tRNA maturation and maintenance system. The CCA end, added to the tRNA by the CCA tRNA nucleotidyltransferase, is the site of aminoacylation, and aminoacyl tRNA synthetases fuse the individual amino acids to the ribose moiety of the terminal A residue. Secondly, the CCA terminus is required for the correct positioning of the aminoacyl-tRNA in the ribosome's A- and P-site in order to guarantee an efficient peptidyl transfer reaction. The CCA-adding enzyme represents an essential activity in the majority of organisms	Thermus thermophilus
physiological function	CCA-adding enzymes represent vital components of the cell's tRNA maturation and maintenance system. The CCA end, added to the tRNA by the CCA tRNA nucleotidyltransferase, is the site of aminoacylation, and aminoacyl tRNA synthetases fuse the individual amino acids to the ribose moiety of the terminal A residue. Secondly, the CCA terminus is required for the correct positioning of the aminoacyl-tRNA in the ribosome's A- and P-site in order to guarantee an efficient peptidyl transfer reaction. The CCA-adding enzyme represents an essential activity in the majority of organisms	Homo sapiens
physiological function	CCA-adding enzymes represent vital components of the cell's tRNA maturation and maintenance system. The CCA end, added to the tRNA by the CCA tRNA nucleotidyltransferase, is the site of aminoacylation, and aminoacyl tRNA synthetases fuse the individual amino acids to the ribose moiety of the terminal A residue. Secondly, the CCA terminus is required for the correct positioning of the aminoacyl-tRNA in the ribosome's A- and P-site in order to guarantee an efficient peptidyl transfer reaction. The CCA-adding enzyme represents an essential activity in the majority of organisms	Geobacillus stearothermophilus
physiological function	CCA-adding enzymes represent vital components of the cell's tRNA maturation and maintenance system. The CCA end, added to the tRNA by the CCA tRNA nucleotidyltransferase, is the site of aminoacylation, and aminoacyl tRNA synthetases fuse the individual amino acids to the ribose moiety of the terminal A residue. Secondly, the CCA terminus is required for the correct positioning of the aminoacyl-tRNA in the ribosome's A- and P-site in order to guarantee an efficient peptidyl transfer reaction. The CCA-adding enzyme represents an essential activity in the majority of organisms	Saccharolobus shibatae
physiological function	CCA-adding enzymes represent vital components of the cell's tRNA maturation and maintenance system. The CCA end, added to the tRNA by the CCA tRNA nucleotidyltransferase, is the site of aminoacylation, and aminoacyl tRNA synthetases fuse the individual amino acids to the ribose moiety of the terminal A residue. Secondly, the CCA terminus is required for the correct positioning of the aminoacyl-tRNA in the ribosome's A- and P-site in order to guarantee an efficient peptidyl transfer reaction. The CCA-adding enzyme represents an essential activity in the majority of organisms	Thermotoga maritima