2qm7

[[Image:2qm7.jpg|left|200px]]<br /><applet load="2qm7" size="350" color="white" frame="true" align="right" spinBox="true"

caption="2qm7, resolution 1.85&Aring;" />

'''MeaB, A Bacterial Homolog of MMAA, Bound to GDP'''<br />

==Overview==

MeaB is an auxiliary protein that plays a crucial role in the protection, and assembly of the B(12)-dependent enzyme methylmalonyl-CoA mutase., Impairments in the human homologue of MeaB, MMAA, lead to methylmalonic, aciduria, an inborn error of metabolism. To explore the role of this, metallochaperone, its structure was solved in the nucleotide-free form, as, well as in the presence of product, GDP. MeaB is a homodimer, with each, subunit containing a central alpha/beta-core G domain that is typical of, the GTPase family, as well as alpha-helical extensions at the N and C, termini that are not found in other metalloenzyme chaperone GTPases. The, C-terminal extension appears to be essential for nucleotide-independent, dimerization, and the N-terminal region is implicated in protein-protein, interaction with its partner protein, methylmalonyl-CoA mutase. The, structure of MeaB confirms that it is a member of the G3E family of P-loop, GTPases, which contains other putative metallochaperones HypB, CooC, and, UreG. Interestingly, the so-called switch regions, responsible for signal, transduction following GTP hydrolysis, are found at the dimer interface of, MeaB instead of being positioned at the surface of the protein where its, partner protein methylmalonyl-CoA mutase should bind. This observation, suggests a large conformation change of MeaB must occur between the GDP-, and GTP-bound forms of this protein. Because of their high sequence, homology, the missense mutations in MMAA that result in methylmalonic, aciduria have been mapped onto MeaB and, in conjunction with mutagenesis, data, provide possible explanations for the pathology of this disease.

 

==About this Structure==

2QM7 is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Methylobacterium_extorquens Methylobacterium extorquens] with <scene name='pdbligand=PO4:'>PO4</scene> and <scene name='pdbligand=GDP:'>GDP</scene> as [http://en.wikipedia.org/wiki/ligands ligands]. Known structural/functional Sites: <scene name='pdbsite=AC1:Po4 Binding Site For Residue A 500'>AC1</scene>, <scene name='pdbsite=AC2:Po4 Binding Site For Residue A 501'>AC2</scene>, <scene name='pdbsite=AC3:Gdp Binding Site For Residue A 601'>AC3</scene> and <scene name='pdbsite=AC4:Gdp Binding Site For Residue B 602'>AC4</scene>. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2QM7 OCA].

 

Crystal structure and mutagenesis of the metallochaperone MeaB: insight into the causes of methylmalonic aciduria., Hubbard PA, Padovani D, Labunska T, Mahlstedt SA, Banerjee R, Drennan CL, J Biol Chem. 2007 Oct 26;282(43):31308-16. Epub 2007 Aug 28. PMID:[http://ispc.weizmann.ac.il//pmbin/getpm?pmid=17728257 17728257]

[[Category: Single protein]]

[[Category: Banerjee, R.]]

[[Category: Drennan, C.L.]]

[[Category: Hubbard, P.A.]]

[[Category: Labunska, T.]]

[[Category: Mahlstedt, S.A.]]

[[Category: Padovani, D.]]

[[Category: GDP]]

[[Category: PO4]]

[[Category: g protein]]

[[Category: g3e]]

[[Category: gtpase]]

[[Category: metallochaperone]]

 

''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Jan 31 10:59:02 2008''