3iij

From Proteopedia

The structure of hCINAP-ADP complex at 1.76 angstroms resolution.

Structural highlights

3iij is a 1 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:	X-ray diffraction, Resolution 1.76Å
Ligands:	,
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

KAD6_HUMAN Broad-specificity nucleoside monophosphate (NMP) kinase that catalyzes the reversible transfer of the terminal phosphate group between nucleoside triphosphates and monophosphates. AMP and dAMP are the preferred substrates, but CMP and dCMP are also good substrates. IMP is phosphorylated to a much lesser extent. All nucleoside triphosphates ATP, GTP, UTP, CTP, dATP, dCTP, dGTP, and TTP are accepted as phosphate donors. CTP is the best phosphate donor, followed by UTP, ATP, GTP and dCTP. May have a role in nuclear energy homeostasis. Has also ATPase activity. May be involved in regulation of Cajal body (CB) formation.^[1]

Evolutionary Conservation

Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.

Publication Abstract from PubMed

Human coilin interacting nuclear ATPase protein (hCINAP) directly interacts with coilin, a marker protein of Cajal Bodies (CBs), nuclear organelles involved in the maturation of small nuclear ribonucleoproteins UsnRNPs and snoRNPs. hCINAP has previously been designated as an adenylate kinase (AK6), but is very atypical as it exhibits unusually broad substrate specificity, structural features characteristic of ATPase/GTPase proteins (Walker motifs A and B) and also intrinsic ATPase activity. Despite its intriguing structure, unique properties and cellular localization, the enzymatic mechanism and biological function of hCINAP have remained poorly characterized. Here, we offer the first high-resolution structure of hCINAP in complex with the substrate ADP (and dADP), the structure of hCINAP with a sulfate ion bound at the AMP binding site, and the structure of the ternary complex hCINAP-Mg(2+) ADP-Pi. Induced fit docking calculations are used to predict the structure of the hCINAP-Mg(2+) ATP-AMP ternary complex. Structural analysis suggested a functional role for His79 in the Walker B motif. Kinetic analysis of mutant hCINAP-H79G indicates that His79 affects both AK and ATPase catalytic efficiency and induces homodimer formation. Finally, we show that in vivo expression of hCINAP-H79G in human cells is toxic and drastically deregulates the number and appearance of CBs in the cell nucleus. Our findings suggest that hCINAP may not simply regulate nucleotide homeostasis, but may have broader functionality, including control of CB assembly and disassembly in the nucleus of human cells. Proteins 2011;. (c) 2011 Wiley-Liss, Inc.

hCINAP is an atypical mammalian nuclear adenylate kinase with an ATPase motif: Structural and functional studies.,Drakou CE, Malekkou A, Hayes JM, Lederer CW, Leonidas DD, Oikonomakos NG, Lamond AI, Santama N, Zographos SE Proteins. 2011 Sep 14. doi: 10.1002/prot.23186. PMID:22038794^[2]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

References

↑ Ren H, Wang L, Bennett M, Liang Y, Zheng X, Lu F, Li L, Nan J, Luo M, Eriksson S, Zhang C, Su XD. The crystal structure of human adenylate kinase 6: An adenylate kinase localized to the cell nucleus. Proc Natl Acad Sci U S A. 2005 Jan 11;102(2):303-8. Epub 2005 Jan 3. PMID:15630091
↑ Drakou CE, Malekkou A, Hayes JM, Lederer CW, Leonidas DD, Oikonomakos NG, Lamond AI, Santama N, Zographos SE. hCINAP is an atypical mammalian nuclear adenylate kinase with an ATPase motif: Structural and functional studies. Proteins. 2011 Sep 14. doi: 10.1002/prot.23186. PMID:22038794 doi:10.1002/prot.23186