› 7et7

X-ray diffraction
2.61Å resolution

Co-crystal structure of Human Nicotinamide N-methyltransferase (NNMT) with tricyclic small molecule inhibitor JBSNF-000028

Released:
DOI: 10.2210/pdb7et7/pdb
PDB entry 7et7 coloured by chain, front view.
PDB entry 7et7 coloured by chain, side view.
PDB entry 7et7 coloured by chain, top view.
Source organism: Homo sapiens
Primary publication:
Novel tricyclic small molecule inhibitors of Nicotinamide N-methyltransferase for the treatment of metabolic disorders.
Ruf S, Rajagopal S, Kadnur SV, Hallur MS, Rani S, Kristam R, Swaminathan S, Zope BR, Gondrala PK, Swamy I, Putta VPRK, Kandan S, Zech G, Schreuder H, Rudolph C, Elvert R, Czech J, Birudukota S, Siddiqui MA, Anand NN, Mane VS, Dittakavi S, Suresh J, Gosu R, Ramesh M, Yura T, Dhakshinamoorthy S, Kannt A
OpenAccess logo Sci Rep 12 15440 (2022)
PMID: 36104373

Function and Biology Details

Reaction catalysed: 
S-adenosyl-L-methionine + nicotinamide = S-adenosyl-L-homocysteine + 1-methylnicotinamide
Biochemical function:
Biological process:
Cellular component:
Sequence domains:

Structure analysis Details

Assembly composition:
monomeric (preferred)
Assembly name:
PDBe Complex ID:
PDB-CPX-154063 (preferred)
Entry contents:
1 distinct polypeptide molecule
Macromolecule:
Nicotinamide N-methyltransferase Chains: A, B, C, D
Molecule details ›
Chains: A, B, C, D
Length: 281 amino acids
Theoretical weight: 31.24 KDa
Source organism: Homo sapiens
Expression system: Escherichia coli
UniProt:
  • Canonical: P40261 (Residues: 1-261; Coverage: 99%)
Gene name: NNMT
Sequence domains: NNMT/PNMT/TEMT family

Ligands and Environments


Cofactor: Ligand SAH 4 x SAH
1 bound ligand:
Ligand JCU 4 x JCU
No modified residues

Experiments and Validation Details

Entry percentile scores
X-ray source: AUSTRALIAN SYNCHROTRON BEAMLINE MX2
Spacegroup: P1
Unit cell:
a: 60.934Å b: 62.862Å c: 75.6Å
α: 108.031° β: 103.54° γ: 104.252°
R-values:
R R work R free
0.226 0.223 0.283
Expression system: Escherichia coli

Quick links

Citations

3 review citations

NAD+ Homeostasis and NAD+-Consuming Enzymes: Implications for Vascular Health.
Campagna et al. (2023)
2 more

1 mention without citation

Novel tricyclic small molecule inhibitors of Nicotinamide N-methyltransferase for the treatment of metabolic disorders.
Ruf et al. (2022)