DB code: S00549

RLCP classification 3.133.90030.336 : Transfer
CATH domain 3.40.50.620 : Rossmann fold Catalytic domain
E.C. 2.7.7.1
CSA
M-CSA
MACiE

CATH domain Related DB codes (homologues)
3.40.50.620 : Rossmann fold S00314 S00316 S00317 S00318 S00315 T00085 T00249 D00300 M00177 M00178 T00106 T00114

Uniprot Enzyme Name
UniprotKB Protein name Synonyms RefSeq Pfam
O26253 Nicotinamide-nucleotide adenylyltransferase
EC 2.7.7.1
NAD(+) pyrophosphorylase
NAD(+) diphosphorylase
NMN adenylyltransferase
NP_275293.1 (Protein)
NC_000916.1 (DNA/RNA sequence)
PF01467 (CTP_transf_2)
[Graphical View]
Q57961 Nicotinamide-nucleotide adenylyltransferase
EC 2.7.7.1
NAD(+) pyrophosphorylase
NAD(+) diphosphorylase
NMN adenylyltransferase
NP_247520.1 (Protein)
NC_000909.1 (DNA/RNA sequence)
PF01467 (CTP_transf_2)
[Graphical View]

KEGG enzyme name
nicotinamide-nucleotide adenylyltransferase
NAD+ pyrophosphorylase
adenosine triphosphate-nicotinamide mononucleotide transadenylase
ATP:NMN adenylyltransferase
diphosphopyridine nucleotide pyrophosphorylase
nicotinamide adenine dinucleotide pyrophosphorylase
nicotinamide mononucleotide adenylyltransferase
NMN adenylyltransferase

UniprotKB: Accession Number Entry name Activity Subunit Subcellular location Cofactor
O26253 NADM_METTH ATP + nicotinamide ribonucleotide = diphosphate + NAD(+). Homohexamer. Cytoplasm (By similarity).
Q57961 NADM_METJA ATP + nicotinamide ribonucleotide = diphosphate + NAD(+). Homohexamer. Cytoplasm.

KEGG Pathways
Map code Pathways E.C.
MAP00760 Nicotinate and nicotinamide metabolism

Compound table
Cofactors Substrates Products Intermediates
KEGG-id C00305 C00002 C00455 C00013 C00003
E.C.
Compound Magnesium ATP Nicotinamide D-ribonucleotide Pyrophosphate NAD+
Type divalent metal (Ca2+, Mg2+) amine group,nucleotide amide group,nucleotide phosphate group/phosphate ion amide group,amine group,nucleotide
ChEBI 18420
 18420
 		15422
 15422
 		16171
 16171
 		29888
 29888
 		15846
 15846
PubChem 888
 888
 		5957
 5957
 		14180
 14180
 		1023
 21961011
 1023
 21961011
 		5893
 5893
1ej2A Unbound Unbound Unbound Analogue:SO4 Bound:NAD
1hybA Unbound Unbound Bound:NMN Unbound Unbound
1m8fA Unbound Unbound Unbound Unbound Bound:NAD
1m8gA Unbound Unbound Unbound Unbound Bound:NAD
1m8jA Unbound Unbound Unbound Analogue:SO4 Bound:NAD
1m8kA Unbound Unbound Unbound Analogue:SO4 Bound:NAD
1m8kB Unbound Unbound Unbound Analogue:SO4 Bound:NAD
1m8kC Unbound Unbound Unbound Analogue:SO4 Bound:NAD
1f9aA Bound:_MG Bound:ATP Unbound Unbound Unbound
1f9aB Bound:_MG Bound:ATP Unbound Unbound Unbound
1f9aC Bound:_MG Bound:ATP Unbound Unbound Unbound
1f9aD Bound:_MG Bound:ATP Unbound Unbound Unbound
1f9aE Bound:_MG Bound:ATP Unbound Unbound Unbound
1f9aF Bound:_MG Bound:ATP Unbound Unbound Unbound

Reference for Active-site residues
resource references E.C.
literature [1], [3], [4]

Active-site residues
PDB Catalytic residues Cofactor-binding residues Modified residues Main-chain involved in catalysis Comment
1ej2A ARG 11;HIS 16;HIS 19;ARG 127;ARG 136 THR 133
1hybA ARG 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
1m8jA ARG 11;HIS 16;HIS 19;ARG 127; THR 133 mutant R136A
1m8kA ARG 11;HIS 16; ;ARG 127;ARG 136 THR 133 mutant H19A
1m8kB ARG 11;HIS 16; ;ARG 127;ARG 136 THR 133 mutant H19A
1m8kC ARG 11;HIS 16; ;ARG 127;ARG 136 THR 133 mutant H19A
1f9aA ARG 8;HIS 13;HIS 16;ARG 121;ARG 130 THR 127
1f9aB ARG 8;HIS 13;HIS 16;ARG 121;ARG 130 THR 127
1f9aC ARG 8;HIS 13;HIS 16;ARG 121;ARG 130 THR 127
1f9aD ARG 8;HIS 13;HIS 16;ARG 121;ARG 130 THR 127
1f9aE ARG 8;HIS 13;HIS 16;ARG 121;ARG 130 THR 127
1f9aF ARG 8;HIS 13;HIS 16;ARG 121;ARG 130 THR 127

References for Catalytic Mechanism
References Sections No. of steps in catalysis
[1]
p.999-1001
[3]
p.7231
[4]
p.34361-34363

References
[1]
Resource
Comments
Medline ID
PubMed ID 10986466
Journal Structure Fold Des
Year 2000
Volume 8
Pages 993-1004
Authors D'Angelo I, Raffaelli N, Dabusti V, Lorenzi T, Magni G, Rizzi M
Title Structure of nicotinamide mononucleotide adenylyltransferase: a key enzyme in NAD(+) biosynthesis.
Related PDB 1f9a
Related UniProtKB
[2]
Resource
Comments
Medline ID
PubMed ID 11017201
Journal Nat Struct Biol
Year 2000
Volume 7
Pages 903-9
Authors Christendat 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
Title Structural proteomics of an archaeon.
Related PDB
Related UniProtKB O26253
[3]
Resource
Comments
Medline ID
PubMed ID 11063748
Journal J Biol Chem
Year 2001
Volume 276
Pages 7225-32
Authors Saridakis V, Christendat D, Kimber MS, Dharamsi A, Edwards AM, Pai EF
Title Insights into ligand binding and catalysis of a central step in NAD+ synthesis: structures of Methanobacterium thermoautotrophicum NMN adenylyltransferase complexes.
Related PDB 1ej2 1hyb
Related UniProtKB
[4]
Resource
Comments
Medline ID
PubMed ID 12810729
Journal J Biol Chem
Year 2003
Volume 278
Pages 34356-63
Authors Saridakis V, Pai EF
Title Mutational, structural, and kinetic studies of the ATP-binding site of Methanobacterium thermoautotrophicum nicotinamide mononucleotide adenylyltransferase.
Related PDB 1m8f 1m8g 1m8j 1m8k
Related UniProtKB

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].

Created Updated
2002-05-02 2010-05-21