DB code: S00316

RLCP classification 3.133.90030.381 : 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 S00549 S00317 S00318 S00315 T00085 T00249 D00300 M00177 M00178 T00106 T00114

Uniprot Enzyme Name
UniprotKB Protein name Synonyms RefSeq Pfam
Q9HAN9 Nicotinamide mononucleotide adenylyltransferase 1
NMN adenylyltransferase 1
EC 2.7.7.1
NP_073624.2 (Protein)
NM_022787.3 (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
Q9HAN9 NMNA1_HUMAN ATP + nicotinamide ribonucleotide = diphosphate + NAD(+). Homohexamer. Interacts with ADPRT/PARP1. Nucleus. Divalent metal cations. Magnesium confers the highest activity.

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
15422
16171
29888
15846
PubChem 888
5957
14180
1023
21961011
5893
1gzuA Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound Bound:NMN Unbound Unbound
1gzuB Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound Bound:NMN Unbound Unbound
1gzuC Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound Bound:NMN Unbound Unbound
1kkuA Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound Unbound Unbound Unbound
1kqnA Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound Unbound Unbound Bound:NAD
1kqnB Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound Unbound Unbound Bound:NAD
1kqnC Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound Unbound Unbound Bound:NAD
1kqnD Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound Unbound Unbound Bound:NAD
1kqnE Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound Unbound Unbound Bound:NAD
1kqnF Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound Unbound Unbound Bound:NAD
1kqoA Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound Unbound Unbound Analogue:DND
1kqoB Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound Unbound Unbound Analogue:DND
1kqoC Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound Unbound Unbound Analogue:DND
1kqoD Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound Unbound Unbound Analogue:DND
1kqoE Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound Unbound Unbound Analogue:DND
1kqoF Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound Unbound Unbound Analogue:DND
1kr2A Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound Unbound Unbound Analogue:TAD
1kr2B Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound Unbound Unbound Analogue:TAD
1kr2C Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound Unbound Unbound Analogue:TAD
1kr2D Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound Unbound Unbound Analogue:TAD
1kr2E Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound Unbound Unbound Analogue:TAD
1kr2F Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound Unbound Unbound Analogue:TAD

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

Active-site residues
PDB Catalytic residues Cofactor-binding residues Modified residues Main-chain involved in catalysis Comment
1gzuA Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain HIS 24;LYS 57;ARG 227 SER 16
1gzuB Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain HIS 24;LYS 57;ARG 227 SER 16
1gzuC Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain HIS 24;LYS 57;ARG 227 SER 16
1kkuA Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain HIS 24;LYS 57;ARG 227 SER 16
1kqnA Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain HIS 24;LYS 57;ARG 227 SER 16
1kqnB Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain HIS 24;LYS 57;ARG 227 SER 16
1kqnC Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain HIS 24;LYS 57;ARG 227 SER 16
1kqnD Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain HIS 24;LYS 57;ARG 227 SER 16
1kqnE Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain HIS 24;LYS 57;ARG 227 SER 16
1kqnF Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain HIS 24;LYS 57;ARG 227 SER 16
1kqoA Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain HIS 24;LYS 57;ARG 227 SER 16
1kqoB Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain HIS 24;LYS 57;ARG 227 SER 16
1kqoC Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain HIS 24;LYS 57;ARG 227 SER 16
1kqoD Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain HIS 24;LYS 57;ARG 227 SER 16
1kqoE Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain HIS 24;LYS 57;ARG 227 SER 16
1kqoF Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain HIS 24;LYS 57;ARG 227 SER 16
1kr2A Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain HIS 24;LYS 57;ARG 227 SER 16
1kr2B Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain HIS 24;LYS 57;ARG 227 SER 16
1kr2C Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain HIS 24;LYS 57;ARG 227 SER 16
1kr2D Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain HIS 24;LYS 57;ARG 227 SER 16
1kr2E Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain HIS 24;LYS 57;ARG 227 SER 16
1kr2F Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain HIS 24;LYS 57;ARG 227 SER 16

References for Catalytic Mechanism
References Sections No. of steps in catalysis
[1]
p.8527-8529
[5]
p.13508-13509

References
[1]
Resource
Comments
Medline ID
PubMed ID 11751893
Journal J Biol Chem
Year 2002
Volume 277
Pages 8524-30
Authors Garavaglia S, D'Angelo I, Emanuelli M, Carnevali F, Pierella F, Magni G, Rizzi M
Title Structure of human NMN adenylyltransferase. A key nuclear enzyme for NAD homeostasis.
Related PDB 1kku
Related UniProtKB
[2]
Resource
Comments
Medline ID
PubMed ID 11788603
Journal J Biol Chem
Year 2002
Volume 277
Pages 13148-54
Authors Zhou T, Kurnasov O, Tomchick DR, Binns DD, Grishin NV, Marquez VE, Osterman AL, Zhang H
Title Structure of human nicotinamide/nicotinic acid mononucleotide adenylyltransferase. Basis for the dual substrate specificity and activation of the oncolytic agent tiazofurin.
Related PDB 1kqn 1kqo 1kr2
Related UniProtKB
[3]
Resource
Comments
Medline ID
PubMed ID 11959140
Journal FEBS Lett
Year 2002
Volume 516
Pages 239-44
Authors Werner E, Ziegler M, Lerner F, Schweiger M, Heinemann U
Title Crystal structure of human nicotinamide mononucleotide adenylyltransferase in complex with NMN.
Related PDB 1gzu
Related UniProtKB
[4]
Resource
Comments
Medline ID
PubMed ID 12068016
Journal J Biol Chem
Year 2002
Volume 277
Pages 33291-9
Authors Singh SK, Kurnasov OV, Chen B, Robinson H, Grishin NV, Osterman AL, Zhang H
Title Crystal structure of Haemophilus influenzae NadR protein. A bifunctional enzyme endowed with NMN adenyltransferase and ribosylnicotinimide kinase activities.
Related PDB
Related UniProtKB
[5]
Resource
Comments
Medline ID
PubMed ID 12574164
Journal J Biol Chem
Year 2003
Volume 278
Pages 13503-11
Authors Zhang X, Kurnasov OV, Karthikeyan S, Grishin NV, Osterman AL, Zhang H
Title Structural characterization of a human cytosolic NMN/NaMN adenylyltransferase and implication in human NAD biosynthesis.
Related PDB
Related UniProtKB

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).

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