View source for 2fli

[[Image:2fli.gif|left|200px]]<br /><applet load="2fli" size="350" color="white" frame="true" align="right" spinBox="true" 
caption="2fli, resolution 1.80&Aring;" />
'''The crystal structure of D-ribulose 5-phosphate 3-epimerase from Streptococus pyogenes complexed with D-xylitol 5-phosphate'''<br />

==Overview==
The "ribulose phosphate binding" superfamily defined by the Structural, Classification of Proteins (SCOP) database is considered the result of, divergent evolution from a common (beta/alpha)(8)-barrel ancestor. The, superfamily includes d-ribulose 5-phosphate 3-epimerase (RPE), orotidine, 5'-monophosphate decarboxylase (OMPDC), and 3-keto-l-gulonate 6-phosphate, decarboxylase (KGPDC), members of the OMPDC suprafamily, as well as, enzymes involved in histidine and tryptophan biosynthesis that utilize, phosphorylated metabolites as substrates. We now report studies of the, functional and structural relationships of RPE to the members of the, superfamily. As suggested by the results of crystallographic studies of, the RPEs from rice [Jelakovic, S., Kopriva, S., Suss, K. H., and Schulz, G. E. (2003) J. Mol. Biol. 326, 127-35] and Plasmodium falciparum, [Caruthers, J., Bosch, J., Bucker, F., Van Voorhis, W., Myler, P., Worthey, E., Mehlin, C., Boni, E., De Titta, G., Luft, J., Kalyuzhniy, O., Anderson, L., Zucker, F., Soltis, M., and Hol, W. G. J. (2006) Proteins, 62, 338-42], the RPE from Streptococcus pyogenes is activated by Zn(2+), which binds with a stoichiometry of one ion per polypeptide. Although wild, type RPE has a high affinity for Zn(2+) and inactive apoenzyme cannot be, prepared, the affinity for Zn(2+) is decreased by alanine substitutions, for the two histidine residues that coordinate the Zn(2+) ion (H34A and, H67A); these mutant proteins can be prepared in an inactive, metal-free, form and activated by exogenous Zn(2+). The crystal structure of the RPE, was solved at 1.8 A resolution in the presence of d-xylitol 5-phosphate, an inert analogue of the d-xylulose 5-phosphate substrate. This structure, suggests that the 2,3-enediolate intermediate in the 1,1-proton transfer, reaction is stabilized by bidentate coordination to the Zn(2+) that also, is liganded to His 34, Asp 36, His 67, and Asp 176; the carboxylate groups, of the Asp residues are positioned also to function as the acid/base, catalysts. Although the conformation of the bound analogue resembles those, of ligands bound in the active sites of OMPDC and KGPDC, the identities of, the active site residues that coordinate the essential Zn(2+) and, participate as acid/base catalysts are not conserved. We conclude that, only the phosphate binding motif located at the ends of the seventh and, eighth beta-strands of the (beta/alpha)(8)-barrel is functionally, conserved among RPE, OMPDC, and KGPDC, consistent with the hypothesis that, the members of the "ribulose phosphate binding" (beta/alpha)(8)-barrel, "superfamily" as defined by SCOP have not evolved by evolutionary, processes involving the intact (beta/alpha)(8)-barrel. Instead, this, "superfamily" may result from assembly from smaller modules, including the, conserved phosphate binding motif associated with the C-terminal, (beta/alpha)(2)-quarter barrel.

==About this Structure==
2FLI is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Streptococcus_pyogenes Streptococcus pyogenes] with <scene name='pdbligand=ZN:'>ZN</scene> and <scene name='pdbligand=DX5:'>DX5</scene> as [http://en.wikipedia.org/wiki/ligands ligands]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2FLI OCA]. 

==Reference==
D-Ribulose 5-phosphate 3-epimerase: functional and structural relationships to members of the ribulose-phosphate binding (beta/alpha)8-barrel superfamily., Akana J, Fedorov AA, Fedorov E, Novak WR, Babbitt PC, Almo SC, Gerlt JA, Biochemistry. 2006 Feb 28;45(8):2493-503. PMID:[http://ispc.weizmann.ac.il//pmbin/getpm?pmid=16489742 16489742]
[[Category: Single protein]]
[[Category: Streptococcus pyogenes]]
[[Category: Akana, J.]]
[[Category: Almo, S.C.]]
[[Category: Fedorov, A.A.]]
[[Category: Fedorov, E.V.]]
[[Category: Gerlt, J.A.]]
[[Category: DX5]]
[[Category: ZN]]
[[Category: (beta/alpha)8-barrel]]
[[Category: d-ribulose 5-phosphate 3-epimerase]]
[[Category: d-xylitol 5-phosphate]]

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