1kku
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(New page: 200px<br /> <applet load="1kku" size="450" color="white" frame="true" align="right" spinBox="true" caption="1kku, resolution 2.5Å" /> '''Crystal structure of...)
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Revision as of 15:45, 12 November 2007
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Crystal structure of nuclear human nicotinamide mononucleotide adenylyltransferase
Overview
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.
About this Structure
1KKU is a Single protein structure of sequence from Homo sapiens. Active as Nicotinamide-nucleotide adenylyltransferase, with EC number 2.7.7.1 Full crystallographic information is available from OCA.
Reference
Structure of human NMN adenylyltransferase. A key nuclear enzyme for NAD homeostasis., Garavaglia S, D'Angelo I, Emanuelli M, Carnevali F, Pierella F, Magni G, Rizzi M, J Biol Chem. 2002 Mar 8;277(10):8524-30. Epub 2001 Dec 19. PMID:11751893
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