EzCatDB: S00549
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DB codeS00549
RLCP classification3.133.90030.336 : Transfer
CATH domainDomain 13.40.50.620 : Rossmann foldCatalytic domain
E.C.2.7.7.1

CATH domainRelated DB codes (homologues)
3.40.50.620 : Rossmann foldS00314,S00316,S00317,S00318,S00315,T00085,T00249,D00300,M00177,M00178,T00106,T00114

Enzyme Name
UniProtKBKEGG

O26253Q57961
Protein nameNicotinamide-nucleotide adenylyltransferaseNicotinamide-nucleotide adenylyltransferasenicotinamide-nucleotide adenylyltransferase
NAD+ pyrophosphorylase
adenosine triphosphate-nicotinamide mononucleotide transadenylase
ATP:NMN adenylyltransferase
diphosphopyridine nucleotide pyrophosphorylase
nicotinamide adenine dinucleotide pyrophosphorylase
nicotinamide mononucleotide adenylyltransferase
NMN adenylyltransferase
SynonymsEC 2.7.7.1
NAD(+) pyrophosphorylase
NAD(+) diphosphorylase
NMN adenylyltransferase
EC 2.7.7.1
NAD(+) pyrophosphorylase
NAD(+) diphosphorylase
NMN adenylyltransferase
RefSeqNP_275293.1 (Protein)
NC_000916.1 (DNA/RNA sequence)
NP_247520.1 (Protein)
NC_000909.1 (DNA/RNA sequence)
PfamPF01467 (CTP_transf_2)
[Graphical view]
PF01467 (CTP_transf_2)
[Graphical view]

KEGG pathways
MAP codePathways
MAP00760Nicotinate and nicotinamide metabolism

UniProtKB:Accession NumberO26253Q57961
Entry nameNADM_METTHNADM_METJA
ActivityATP + nicotinamide ribonucleotide = diphosphate + NAD(+).ATP + nicotinamide ribonucleotide = diphosphate + NAD(+).
SubunitHomohexamer.Homohexamer.
Subcellular locationCytoplasm (By similarity).Cytoplasm.
Cofactor


Compound table: links to PDB-related databases & PoSSuM

CofactorsSubstratesProducts
KEGG-idC00305C00002C00455C00013C00003
CompoundMagnesiumATPNicotinamide D-ribonucleotidePyrophosphateNAD+
Typedivalent metal (Ca2+, Mg2+)amine group,nucleotideamide group,nucleotidephosphate group/phosphate ionamide group,amine group,nucleotide
ChEBI18420
15422
16171
29888
15846
PubChem888
5957
14180
21961011
1023
5893
             
1ej2AUnboundUnboundUnboundAnalogue:SO4Bound:NAD
1hybAUnboundUnboundBound:NMNUnboundUnbound
1m8fAUnboundUnboundUnboundUnboundBound:NAD
1m8gAUnboundUnboundUnboundUnboundBound:NAD
1m8jAUnboundUnboundUnboundAnalogue:SO4Bound:NAD
1m8kAUnboundUnboundUnboundAnalogue:SO4Bound:NAD
1m8kBUnboundUnboundUnboundAnalogue:SO4Bound:NAD
1m8kCUnboundUnboundUnboundAnalogue:SO4Bound:NAD
1f9aABound:_MGBound:ATPUnboundUnboundUnbound
1f9aBBound:_MGBound:ATPUnboundUnboundUnbound
1f9aCBound:_MGBound:ATPUnboundUnboundUnbound
1f9aDBound:_MGBound:ATPUnboundUnboundUnbound
1f9aEBound:_MGBound:ATPUnboundUnboundUnbound
1f9aFBound:_MGBound:ATPUnboundUnboundUnbound

Active-site residues
resource
literature [1], [3], [4]
pdbCatalytic residuesMain-chain involved in catalysiscomment
           
1ej2AARG 11;HIS 16;HIS 19;ARG 127;ARG 136
THR 133
 
1hybAARG 11;HIS 16;      ;       ;ARG 136
THR 133
mutant H19A, invisible 124-129
1m8fA      ;HIS 16;HIS 19;ARG 127;ARG 136
THR 133
mutant R11A
1m8gA      ;HIS 16;HIS 19;ARG 127;ARG 136
THR 133
mutant R11K
1m8jAARG 11;HIS 16;HIS 19;ARG 127;       
THR 133
mutant R136A
1m8kAARG 11;HIS 16;      ;ARG 127;ARG 136
THR 133
mutant H19A
1m8kBARG 11;HIS 16;      ;ARG 127;ARG 136
THR 133
mutant H19A
1m8kCARG 11;HIS 16;      ;ARG 127;ARG 136
THR 133
mutant H19A
1f9aAARG  8;HIS 13;HIS 16;ARG 121;ARG 130
THR 127
 
1f9aBARG  8;HIS 13;HIS 16;ARG 121;ARG 130
THR 127
 
1f9aCARG  8;HIS 13;HIS 16;ARG 121;ARG 130
THR 127
 
1f9aDARG  8;HIS 13;HIS 16;ARG 121;ARG 130
THR 127
 
1f9aEARG  8;HIS 13;HIS 16;ARG 121;ARG 130
THR 127
 
1f9aFARG  8;HIS 13;HIS 16;ARG 121;ARG 130
THR 127
 

References for Catalytic Mechanism
ReferencesSectionsNo. of steps in catalysis
[1]p.999-1001
[3]p.7231
[4]p.34361-34363

references
[1]
PubMed ID10986466
JournalStructure Fold Des
Year2000
Volume8
Pages993-1004
AuthorsD'Angelo I, Raffaelli N, Dabusti V, Lorenzi T, Magni G, Rizzi M
TitleStructure of nicotinamide mononucleotide adenylyltransferase: a key enzyme in NAD(+) biosynthesis.
Related PDB1f9a
[2]
PubMed ID11017201
JournalNat Struct Biol
Year2000
Volume7
Pages903-9
AuthorsChristendat D, Yee A, Dharamsi A, Kluger Y, Savchenko A, Cort JR, Booth V, Mackereth CD, Saridakis V, Ekiel I, Kozlov G, Maxwell KL, Wu N, McIntosh LP, Gehring K, Kennedy MA, Davidson AR, Pai EF, Gerstein M, Edwards AM, Arrowsmith CH
TitleStructural proteomics of an archaeon.
Related UniProtKBO26253
[3]
PubMed ID11063748
JournalJ Biol Chem
Year2001
Volume276
Pages7225-32
AuthorsSaridakis V, Christendat D, Kimber MS, Dharamsi A, Edwards AM, Pai EF
TitleInsights into ligand binding and catalysis of a central step in NAD+ synthesis: structures of Methanobacterium thermoautotrophicum NMN adenylyltransferase complexes.
Related PDB1ej2,1hyb
[4]
PubMed ID12810729
JournalJ Biol Chem
Year2003
Volume278
Pages34356-63
AuthorsSaridakis V, Pai EF
TitleMutational, structural, and kinetic studies of the ATP-binding site of Methanobacterium thermoautotrophicum nicotinamide mononucleotide adenylyltransferase.
Related PDB1m8f,1m8g,1m8j,1m8k

comments
This enzyme is homologous to the counterpart enzyme (see S00316 in EzCatDB). However, the catalytic residues, which are involved in transition-state stabilization, seem to be different from those from the counterpart enzymes.
According to the literature [1], [3] & [4], the reaction proceeds as follows:
(1) The 5'-phosphate group of NMN makes a nucleophilic attack on the alpha-phosphoryl group of ATP, from the opposite side of the pyrophosphate leaving group (beta- and gamma-phosphate groups).
(2) The transition state seems to be stabilized by the second conserved histidine residue of (T/H)XXH motif, and positively charged residues, such as Arg11 and His19, surrounding the alpha-phosphate group of ATP (or the transferred group). (Probably, the leaving group of ATP also seems to be stabilized by the positively charged residues such as His16, Arg127 and Arg136 as well as mainchain of Thr133.)
(2')Moreover, magnesium ion, which was observed to be bound to the three phosphate groups (alpha-, beta- & gamma-phosphate) in some crystal structures, also plays a role in catalysis, by stabilizing the transition state, and by weakning the alpha-beta phosphate bond of ATP.
Thus, this enzyme active site orients the reacting partners, ATP and NMN, in proper positions for the direct reaction to occur, whilst neither acid/base nor nucleophile from enzyme residues have been implicated in the catalytic reaction [4].

createdupdated
2002-05-022010-05-21


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