EzCatDB: S00316
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DB codeS00316
RLCP classification3.133.90030.381 : 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,S00549,S00317,S00318,S00315,T00085,T00249,D00300,M00177,M00178,T00106,T00114

Enzyme Name
UniProtKBKEGG

Q9HAN9
Protein nameNicotinamide mononucleotide adenylyltransferase 1nicotinamide-nucleotide adenylyltransferase
NAD+ pyrophosphorylase
adenosine triphosphate-nicotinamide mononucleotide transadenylase
ATP:NMN adenylyltransferase
diphosphopyridine nucleotide pyrophosphorylase
nicotinamide adenine dinucleotide pyrophosphorylase
nicotinamide mononucleotide adenylyltransferase
NMN adenylyltransferase
SynonymsNMN adenylyltransferase 1
EC 2.7.7.1
RefSeqNP_073624.2 (Protein)
NM_022787.3 (DNA/RNA sequence)
PfamPF01467 (CTP_transf_2)
[Graphical view]

KEGG pathways
MAP codePathways
MAP00760Nicotinate and nicotinamide metabolism

UniProtKB:Accession NumberQ9HAN9
Entry nameNMNA1_HUMAN
ActivityATP + nicotinamide ribonucleotide = diphosphate + NAD(+).
SubunitHomohexamer. Interacts with ADPRT/PARP1.
Subcellular locationNucleus.
CofactorDivalent metal cations. Magnesium confers the highest activity.

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
             
1gzuAUnboundUnboundBound:NMNUnboundUnbound
1gzuBUnboundUnboundBound:NMNUnboundUnbound
1gzuCUnboundUnboundBound:NMNUnboundUnbound
1kkuAUnboundUnboundUnboundUnboundUnbound
1kqnAUnboundUnboundUnboundUnboundBound:NAD
1kqnBUnboundUnboundUnboundUnboundBound:NAD
1kqnCUnboundUnboundUnboundUnboundBound:NAD
1kqnDUnboundUnboundUnboundUnboundBound:NAD
1kqnEUnboundUnboundUnboundUnboundBound:NAD
1kqnFUnboundUnboundUnboundUnboundBound:NAD
1kqoAUnboundUnboundUnboundUnboundAnalogue:DND
1kqoBUnboundUnboundUnboundUnboundAnalogue:DND
1kqoCUnboundUnboundUnboundUnboundAnalogue:DND
1kqoDUnboundUnboundUnboundUnboundAnalogue:DND
1kqoEUnboundUnboundUnboundUnboundAnalogue:DND
1kqoFUnboundUnboundUnboundUnboundAnalogue:DND
1kr2AUnboundUnboundUnboundUnboundAnalogue:TAD
1kr2BUnboundUnboundUnboundUnboundAnalogue:TAD
1kr2CUnboundUnboundUnboundUnboundAnalogue:TAD
1kr2DUnboundUnboundUnboundUnboundAnalogue:TAD
1kr2EUnboundUnboundUnboundUnboundAnalogue:TAD
1kr2FUnboundUnboundUnboundUnboundAnalogue:TAD

Active-site residues
resource
literature [3]
pdbCatalytic residuesMain-chain involved in catalysis
          
1gzuAHIS 24;LYS 57;ARG 227
SER 16
1gzuBHIS 24;LYS 57;ARG 227
SER 16
1gzuCHIS 24;LYS 57;ARG 227
SER 16
1kkuAHIS 24;LYS 57;ARG 227
SER 16
1kqnAHIS 24;LYS 57;ARG 227
SER 16
1kqnBHIS 24;LYS 57;ARG 227
SER 16
1kqnCHIS 24;LYS 57;ARG 227
SER 16
1kqnDHIS 24;LYS 57;ARG 227
SER 16
1kqnEHIS 24;LYS 57;ARG 227
SER 16
1kqnFHIS 24;LYS 57;ARG 227
SER 16
1kqoAHIS 24;LYS 57;ARG 227
SER 16
1kqoBHIS 24;LYS 57;ARG 227
SER 16
1kqoCHIS 24;LYS 57;ARG 227
SER 16
1kqoDHIS 24;LYS 57;ARG 227
SER 16
1kqoEHIS 24;LYS 57;ARG 227
SER 16
1kqoFHIS 24;LYS 57;ARG 227
SER 16
1kr2AHIS 24;LYS 57;ARG 227
SER 16
1kr2BHIS 24;LYS 57;ARG 227
SER 16
1kr2CHIS 24;LYS 57;ARG 227
SER 16
1kr2DHIS 24;LYS 57;ARG 227
SER 16
1kr2EHIS 24;LYS 57;ARG 227
SER 16
1kr2FHIS 24;LYS 57;ARG 227
SER 16

References for Catalytic Mechanism
ReferencesSectionsNo. of steps in catalysis
[1]p.8527-8529
[5]p.13508-13509

references
[1]
PubMed ID11751893
JournalJ Biol Chem
Year2002
Volume277
Pages8524-30
AuthorsGaravaglia S, D'Angelo I, Emanuelli M, Carnevali F, Pierella F, Magni G, Rizzi M
TitleStructure of human NMN adenylyltransferase. A key nuclear enzyme for NAD homeostasis.
Related PDB1kku
[2]
PubMed ID11788603
JournalJ Biol Chem
Year2002
Volume277
Pages13148-54
AuthorsZhou T, Kurnasov O, Tomchick DR, Binns DD, Grishin NV, Marquez VE, Osterman AL, Zhang H
TitleStructure of human nicotinamide/nicotinic acid mononucleotide adenylyltransferase. Basis for the dual substrate specificity and activation of the oncolytic agent tiazofurin.
Related PDB1kqn,1kqo,1kr2
[3]
PubMed ID11959140
JournalFEBS Lett
Year2002
Volume516
Pages239-44
AuthorsWerner E, Ziegler M, Lerner F, Schweiger M, Heinemann U
TitleCrystal structure of human nicotinamide mononucleotide adenylyltransferase in complex with NMN.
Related PDB1gzu
[4]
PubMed ID12068016
JournalJ Biol Chem
Year2002
Volume277
Pages33291-9
AuthorsSingh SK, Kurnasov OV, Chen B, Robinson H, Grishin NV, Osterman AL, Zhang H
TitleCrystal structure of Haemophilus influenzae NadR protein. A bifunctional enzyme endowed with NMN adenyltransferase and ribosylnicotinimide kinase activities.
[5]
PubMed ID12574164
JournalJ Biol Chem
Year2003
Volume278
Pages13503-11
AuthorsZhang X, Kurnasov OV, Karthikeyan S, Grishin NV, Osterman AL, Zhang H
TitleStructural characterization of a human cytosolic NMN/NaMN adenylyltransferase and implication in human NAD biosynthesis.

comments
This enzyme is homologous to the archaeon enzyme (see S00549 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] and [5], 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 His24, Lys57 and mainchain amide of Ser16, which are surrounding the alpha-phosphate group of ATP. (Probably, the leaving group of ATP also seems to be stabilized by the positively charged residues such as His24 and Arg227.)
(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 (see S00549 in EzCatDB).

createdupdated
2002-05-022010-05-21


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Funded by BIRD/Japan Science and Technology Corporation (JST) (October 2007 - September 2010)
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