1KKU

Crystal structure of nuclear human nicotinamide mononucleotide adenylyltransferase

Summary for 1KKU

• Entry DOI: 10.2210/pdb1kku/pdb
• Related: 1ej2 1f9a
• Descriptor: NICOTINAMIDE MONONUCLEOTIDE ADENYLYLTRANSFERASE (2 entities in total)
• Functional Keywords: alpha/beta structure - rossmann fold, transferase
• Biological source: Homo sapiens (human)
• Cellular location: Nucleus: Q9HAN9
• Total number of polymer chains: 1
• Total formula weight: 32016.52

Authors

Garavaglia, S.,D'Angelo, I.,Emanuelli, M.,Carnevali, F.,Pierella, F.,Magni, G.,Rizzi, M. (deposition date: 2001-12-10, release date: 2002-06-10, Last modification date: 2024-02-14)

Primary citation

Garavaglia, S.,D'Angelo, I.,Emanuelli, M.,Carnevali, F.,Pierella, F.,Magni, G.,Rizzi, M.
Structure of human NMN adenylyltransferase. A key nuclear enzyme for NAD homeostasis.
J.Biol.Chem., 277:8524-8530, 2002

PubMed Abstract: Nicotinamide mononucleotide adenylyltransferase (NMNAT), a member of the nucleotidyltransferase alpha/beta-phosphodiesterases superfamily, catalyzes a universal step (NMN + ATP = NAD + PP(i)) in NAD biosynthesis. Localized within the nucleus, the activity of the human enzyme is greatly altered in tumor cells, rendering it a promising target for cancer chemotherapy. By using a combination of single isomorphous replacement and density modification techniques, the human NMNAT structure was solved by x-ray crystallography to a 2.5-A resolution, revealing a hexamer that is composed of alpha/beta-topology subunits. The active site topology of the enzyme, analyzed through homology modeling and structural comparison with other NMNATs, yielded convincing evidence for a substrate-induced conformational change. We also observed remarkable structural conservation in the ATP-recognition motifs GXXXPX(T/H)XXH and SXTXXR, which we take to be the universal signature for NMNATs. Structural comparison of human and prokaryotic NMNATs may also lead to the rational design of highly selective antimicrobial drugs.

PubMed: 11751893
DOI: 10.1074/jbc.M111589200

Experimental method

X-RAY DIFFRACTION (2.5 Å)