EzCatDB: D00244
Related links:    PDB-formatted query search system Fasta-formatted query search system Fasta-formatted query search system

DB codeD00244
RLCP classification4.12.18410.92 : Addition
5.201.672500.74 : Elimination
CATH domainDomain 13.40.350.10 : Creatine Amidinohydrolase; Chain A, domain 1
Domain 23.90.230.10 : Creatine AmidinohydrolaseCatalytic domain
E.C.3.5.3.3
CSA1chm
MACiEM0096

CATH domainRelated DB codes (homologues)
3.40.350.10 : Creatine Amidinohydrolase; Chain A, domain 1D00185
3.90.230.10 : Creatine AmidinohydrolaseD00185

Enzyme Name
UniProtKBKEGG

P38488
Protein nameCreatinasecreatinase
SynonymsEC 3.5.3.3
Creatine amidinohydrolase
PfamPF01321 (Creatinase_N)
PF00557 (Peptidase_M24)
[Graphical view]

KEGG pathways
MAP codePathways
MAP00330Arginine and proline metabolism

UniProtKB:Accession NumberP38488
Entry nameCREA_PSEPU
ActivityCreatine + H(2)O = sarcosine + urea.
SubunitHomodimer.
Subcellular location
Cofactor

Compound table: links to PDB-related databases & PoSSuM

SubstratesProductsintermediates
KEGG-idC00300C00001C00213C00086
CompoundCreatineH2OSarcosineUreaTetrahedral intermediate
Typeamino acids,amide group,imine groupH2Oamino acidsamide group,amine group
ChEBI16919
57947
15377
15611
57433
16199
48376

PubChem59098743
586
962
22247451
7311726
1088
1176

             
1chmA01Unbound UnboundUnboundUnbound
1chmB01Unbound UnboundUnboundUnbound
1chmA02Unbound UnboundUnboundIntermediate-analogue:CMS
1chmB02Analogue:CMS UnboundUnboundUnbound

Active-site residues
resource
literature [1], [2]
pdbCatalytic residues
         
1chmA01 
1chmB01 
1chmA02HIS 232;GLU 262;GLU 358
1chmB02HIS 232;GLU 262;GLU 358

References for Catalytic Mechanism
ReferencesSectionsNo. of steps in catalysis
[1]Fig.11, Fig.12, p.430-432
[2]Figure 10, p.6074

references
[1]
CommentsX-RAY CRYSTALLOGRAPHY (1.9 ANGSTROMS).
Medline ID89125596
PubMed ID3221393
JournalJ Mol Biol
Year1988
Volume204
Pages417-33
AuthorsHoeffken HW, Knof SH, Bartlett PA, Huber R, Moellering H, Schumacher G
TitleCrystal structure determination, refinement and molecular model of creatine amidinohydrolase from Pseudomonas putida.
Related UniProtKBP38488
[2]
CommentsX-RAY CRYSTALLOGRAPHY (1.9 ANGSTROMS).
Medline ID90339496
PubMed ID1696320
JournalJ Mol Biol
Year1990
Volume214
Pages597-610
AuthorsColl M, Knof SH, Ohga Y, Messerschmidt A, Huber R, Moellering H, Russmann L, Schumacher G
TitleEnzymatic mechanism of creatine amidinohydrolase as deduced from crystal structures.
Related PDB1chm
Related UniProtKBP38488
[3]
PubMed ID8504814
JournalEur J Biochem
Year1993
Volume213
Pages1225-33
AuthorsSchumann J, Jaenicke R
TitleCreatinase in its collapsed A state shows properties of a molten globule with dimeric quaternary structure.
[4]
PubMed ID8251936
JournalProtein Sci
Year1993
Volume2
Pages1612-20
AuthorsSchumann J, Bohm G, Schumacher G, Rudolph R, Jaenicke R
TitleStabilization of creatinase from Pseudomonas putida by random mutagenesis.
[5]
PubMed ID8291080
JournalTrends Biochem Sci
Year1993
Volume18
Pages403-5
AuthorsMurzin AG
TitleCan homologous proteins evolve different enzymatic activities?
[6]
PubMed ID8146141
JournalProc Natl Acad Sci U S A
Year1994
Volume91
Pages2473-7
AuthorsBazan JF, Weaver LH, Roderick SL, Huber R, Matthews BW
TitleSequence and structure comparison suggest that methionine aminopeptidase, prolidase, aminopeptidase P, and creatinase share a common fold.
[7]
PubMed ID10387007
JournalBiochemistry
Year1999
Volume38
Pages7678-88
AuthorsLowther WT, Orville AM, Madden DT, Lim S, Rich DH, Matthews BW
TitleEscherichia coli methionine aminopeptidase: implications of crystallographic analyses of the native, mutant, and inhibited enzymes for the mechanism of catalysis.

comments
Although this enzyme belongs to the peptidase family-M24, it does not utilize a divalent metal ion as a cofactor.
According to the literature [2], this enzyme catalyzes two successive reactions, addition and elimination, as follows:
(A) Addition of water to double-bond:
(A0) Throughout this reaction, Glu262 and Glu358 stabilize the positive charge on the guanidinium group.
(A1) His232 acts as a general base to deprotonate and activate the water.
(A2) The activated water or hydroxyl group makes a nucleophilic attack on the C(1) carbon of guanidium group (addition site), leading to the formation of tetrahedral intermediate.
(A3) His232 acts as a general acid to protonate the N(3) nitrogen atom (protonation site), forming guanidinium hydrate.
(B) Eliminative double-bond formation:
(B1) His232 acts as a general base to deptoronate guanidinium hydrate (deprotonation site), leading to the cleavage of the covalent bond between C(1) and N(3) atoms.

createdupdated
2006-04-042009-02-26


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 2008)
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)
Funded by Grant-in-Aid for Publication of Scientific Research Results/Japan Society for the Promotion of Science (JSPS) (April 2012 - March 2013)
Supported by the commission for the Development of Artificial Gene Synthesis Technology for Creating Innovative Biomaterial from the Ministry of Economy, Trade and Industry (METI) (October 2012 - )
© Biotechnology Research Institute for Drug Discovery, AIST, 2015-2016 All Rights Reserved.
© Computational Biology Research Center, AIST, 2004-2016 All Rights Reserved.