Crystal structures of monkey and mouse nicotinamide N-methyltransferase (NNMT) bound with end product, 1-methyl nicotinamide

Autor: Saravanakumar Dhakshinamoorthy, Ramachandraiah Gosu, Saravanan Kandan, Herman Schreuder, Suresh Juluri, Raghunadha Reddy Burri, Swarnakumari Birudukota, Aimo Kannt, Christine Rudolph, Shama Shaik, Thomas Langer, Srinivasan Swaminathan, Niranjan Naranapura Anand, Manish Kumar Thakur, Rajendra Kristam, Mahanandeesha S. Hallur, Sridharan Rajagopal, Sven Ruf, Reejuana Parveen
Rok vydání: 2017
Předmět:
0301 basic medicine
Models
Molecular
Niacinamide
Protein Conformation
alpha-Helical
S-Adenosylmethionine
Stereochemistry
Biophysics
Gene Expression
Nicotinamide N-methyltransferase
Crystallography
X-Ray
Biochemistry
Cofactor
Substrate Specificity
03 medical and health sciences
chemistry.chemical_compound
Mice
Catalytic Domain
Escherichia coli
Nicotinamide N-Methyltransferase
Transferase
Animals
Protein Interaction Domains and Motifs
Amino Acid Sequence
Cloning
Molecular
Molecular Biology
Ternary complex
chemistry.chemical_classification
Feedback
Physiological
Methionine
030102 biochemistry & molecular biology
biology
Nicotinamide
Sequence Homology
Amino Acid
Active site
Cell Biology
Macaca mulatta
Recombinant Proteins
Protein Structure
Tertiary
030104 developmental biology
Enzyme
chemistry
biology.protein
Protein Conformation
beta-Strand
Sequence Alignment
Protein Binding
Zdroj: Biochemical and biophysical research communications. 491(2)
ISSN: 1090-2104
Popis: Nicotinamide N-methyltransferase (NNMT) is a S-adenosyl- l -methionine (SAM)-dependent enzyme that catalyzes N-methylation of nicotinamide (NA) and other pyridines to form N-methyl pyridinium ions. Here we report the first ternary complex X-ray crystal structures of monkey NNMT and mouse NNMT in bound form with the primary endogenous product, 1-methyl nicotinamide (MNA) and demethylated cofactor, S-adenosyl-homocysteine (SAH) determined at 2.30 A and 1.88 A respectively. The structural fold of these enzymes is identical to human NNMT. It is known that the primary endogenous product catalyzed by NNMT, MNA is a specific inhibitor of NNMT. Our data clearly indicates that the MNA binds to the active site and it would be trapped in the active site due to the formation of the bridge between the pole (long helix, α3) and long C-terminal loop. This might explain the mechanism of MNA acting as a feedback inhibitor of NNMT.
Databáze: OpenAIRE
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