EzCatDB: D00302

DB codeD00302
RLCP classification3.133.305000.384
3.103.90000.335
CATH domainDomain 13.65.10.20Catalytic domain
Domain 23.30.360.20
E.C.6.5.1.4
CSA1qmh


Enzyme Name
Swiss-protKEGG

P46849
Protein nameRNA 3''-terminal phosphate cyclaseRNA-3'-phosphate cyclase
RNA cyclase
SynonymsRNA-3''-phosphate cyclase
RNA cyclase
EC 6.5.1.4


Swiss-prot:Accession NumberP46849
Entry nameRTCA_ECOLI
ActivityATP + RNA 3''-terminal-phosphate = AMP + diphosphate + RNA terminal-2'',3''-cyclic-phosphate.
SubunitHomodimer, disulfide-linked.
Subcellular locationCytoplasm.
Cofactor


CofactorsSubstratesProducts
KEGG-idC00305C00002C03638C00013C00020C04312
CompoundMagnesiumATPRNA 3'-terminal-phosphatePyrophosphateAMPRNA terminal-2',3'-cyclic-phosphate
Typedivalent metal (Ca2+, Mg2+)amine group,nucleotidenucleic acidsphosphate group/phosphate ionamine group,nucleotidenucleic acids
1qmhA01UnboundUnboundAnalogue:CITUnboundUnboundUnbound
1qmhB01UnboundUnboundAnalogue:CITUnboundUnboundUnbound
1qmiA01UnboundUnboundUnboundUnboundUnboundUnbound
1qmiB01UnboundUnboundUnboundUnboundUnboundUnbound
1qmiC01UnboundUnboundUnboundUnboundUnboundUnbound
1qmiD01UnboundUnboundUnboundUnboundUnboundUnbound
1qmhA02UnboundUnboundUnboundUnboundUnboundUnbound
1qmhB02UnboundUnboundUnboundUnboundUnboundUnbound
1qmiA02UnboundUnboundUnboundUnboundUnboundUnbound
1qmiB02UnboundUnboundUnboundUnboundUnboundUnbound
1qmiC02UnboundUnboundUnboundUnboundUnboundUnbound
1qmiD02UnboundUnboundUnboundUnboundUnboundUnbound

Active-site residues
resource
literature [7]
pdbCatalytic residuesMain-chain involved in catalysis
1qmhA01GLU 14;GLN 18;ARG 21;ARG 40;ARG 43;GLN 51;HIS 52;HIS 309
GLY 17
1qmhB01GLU 14;GLN 18;ARG 21;ARG 40;ARG 43;GLN 51;HIS 52;HIS 309
GLY 17
1qmiA01GLU 14;GLN 18;ARG 21;ARG 40;ARG 43;GLN 51;HIS 52;HIS 309
GLY 17
1qmiB01GLU 14;GLN 18;ARG 21;ARG 40;ARG 43;GLN 51;HIS 52;HIS 309
GLY 17
1qmiC01GLU 14;GLN 18;ARG 21;ARG 40;ARG 43;GLN 51;HIS 52;HIS 309
GLY 17
1qmiD01GLU 14;GLN 18;ARG 21;ARG 40;ARG 43;GLN 51;HIS 52;HIS 309
GLY 17
1qmhA02

1qmhB02

1qmiA02

1qmiB02

1qmiC02

1qmiD02


References for Catalytic Mechanism
ReferencesSectionsNo. of steps in catalysis
[3]

[5]

[7]


references
[1]
PubMed ID2579395
JournalProc Natl Acad Sci U S A
Year1985
Volume82
Pages1316-20
AuthorsFilipowicz W, Strugala K, Konarska M, Shatkin AJ
TitleCyclization of RNA 3'-terminal phosphate by cyclase from HeLa cells proceeds via formation of N(3')pp(5')A activated intermediate.
[2]
PubMed ID2199762
JournalMethods Enzymol
Year1990
Volume181
Pages499-510
AuthorsFilipowicz W, Vicente O
TitleRNA 3'-terminal phosphate cyclase from HeLa cells.
[3]
CommentsREVISION, AND CHARACTERIZATION
Medline ID97327572
PubMed ID9184239
JournalEMBO J
Year1997
Volume16
Pages2955-67
AuthorsGenschik P, Billy E, Swianiewicz M, Filipowicz W
TitleThe human RNA 3'-terminal phosphate cyclase is a member of a new family of proteins conserved in Eucarya, Bacteria and Archaea.
Related Swiss-protP46849
[4]
PubMed ID10397337
JournalActa Biochim Pol
Year1998
Volume45
Pages895-906
AuthorsFilipowicz W, Billy E, Drabikowski K, Genschik P
TitleCyclases of the 3'-terminal phosphate in RNA: a new family of RNA processing enzymes conserved in eucarya, bacteria and archaea.
[5]
CommentsCHARACTERIZATION
Medline ID98411361
PubMed ID9738023
JournalJ Biol Chem
Year1998
Volume273
Pages25516-26
AuthorsGenschik P, Drabikowski K, Filipowicz W
TitleCharacterization of the Escherichia coli RNA 3'-terminal phosphate cyclase and its sigma54-regulated operon.
Related Swiss-protP46849
[6]
PubMed ID10574971
JournalJ Biol Chem
Year1999
Volume274
Pages34955-60
AuthorsBilly E, Hess D, Hofsteenge J, Filipowicz W
TitleCharacterization of the adenylation site in the RNA 3'-terminal phosphate cyclase from Escherichia coli.
[7]
CommentsX-RAY CRYSTALLOGRAPHY (2.1 ANGSTROMS)
Medline ID20139688
PubMed ID10673421
JournalStructure Fold Des
Year2000
Volume8
Pages13-23
AuthorsPalm GJ, Billy E, Filipowicz W, Wlodawer A
TitleCrystal structure of RNA 3'-terminal phosphate cyclase, a ubiquitous enzyme with unusual topology.
Related PDB1qmh,1qmi
Related Swiss-protP46849

comments
This enzyme catalyzes two successive transfer reactions, an AMP transfer and an intramolecular phosphoryl transfer. Although the detailed mechanism remains unclear, the reactions may proceed in the following way (see [1], [3] & [7]).
(A) The AMP transfer reaction proceeds through an adenylated-enzyme intermediate.
(1) His309 makes a nucleophilic attack on the gamma-phosphate of ATP (the first substrate), to form an adenylated histidine residue as an intermediate, releasing pyrophosphate (originally, gamma- and beta-phosphate groups of ATP) as a leaving group. Here, Glu14 probably activates His309 by acting as a general base to abstract proton from the residue, considering the active-site structure (see [7]). During the reaction, cofactor magnesium ion and Arginine/Histidine/Glutamine cluster and main chain (composed of Gly17, Gln18, Arg21, Arg40, Arg43 and His52) stabilize the transition state.
(2) As the acceptor group, 3'-terminal phosphate of the second substrate, RNA, makes a nucleophilic attack on the phosphoryl group of the adenylated histidine, to form the second intermediate, RNA-N(3')pp(5')A.
(B) The intramolecular phosphoryl transfer to 2'-OH may occur spontaneously (see [3]).
(1') The adjacent 2'-OH group, as the second acceptor group, makes a nucleophilic attack on the phosphorus atom in the phosphodiester linkage, releasing AMP as a leaving group. During this reaction, cofactor magnesium ion and Arginine/Histidine/Glutamine cluster and main chain (composed of Gly17, Gln18, Arg21, Arg40, Arg43 and His52) may also stabilize the transition state.
As magnesium ion binding site has not been elucidated yet, it might be bound directly to the phosphate groups of ATP or AMP.

createdupdated
2004-10-222009-02-26
Copyright: Nozomi Nagano, JST & CBRC-AIST
Funded by PRESTO/Japan Science and Technology Corporation (JST) (December 2001 - November 2004)
Funded by Grant-in-Aid for Publication of Scientific Research Results/Japan Society for the Promotion of Science (JSPS) (April 2005 - March 2006)
Funded by Grant-in-Aid for Scientific Research (B)/Japan Society for the Promotion of Science (JSPS) (April 2005 - March 2008)
Funded by BIRD/Japan Science and Technology Corporation (JST) (September 2005 - September 2010)
Funded by BIRD/Japan Science and Technology Corporation (JST) (October 2007 - September 2010)
Funded by Grant-in-Aid for Publication of Scientific Research Results/Japan Society for the Promotion of Science (JSPS) (April 2011 - March 2012)

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