View source for 2iof

[[Image:2iof.jpg|left|200px]]<br /><applet load="2iof" size="450" color="white" frame="true" align="right" spinBox="true" 
caption="2iof, resolution 2.500&Aring;" />
'''Crystal structure of phosphonoacetaldehyde hydrolase with sodium borohydride-reduced substrate intermediate'''<br />

==Overview==
Phosphonatase functions in the 2-aminoethylphosphonate (AEP) degradation, pathway of bacteria, catalyzing the hydrolysis of the C-P bond in, phosphonoacetaldehyde (Pald) via formation of a bi-covalent, Lys53ethylenamine/Asp12 aspartylphosphate intermediate. Because, phosphonatase is a member of the haloacid dehalogenase superfamily, a, family predominantly comprised of phosphatases, the question arises as to, how this new catalytic activity evolved. The source of general acid-base, catalysis for Schiff-base formation and aspartylphosphate hydrolysis was, probed using pH-rate profile analysis of active-site mutants and X-ray, crystallographic analysis of modified forms of the enzyme. The 2.9 A X-ray, crystal structure of the mutant Lys53Arg complexed with Mg2+ and phosphate, shows that the equilibrium between the open and the closed conformation is, disrupted, favoring the open conformation. Thus, proton dissociation from, the cap domain Lys53 is required for cap domain-core domain closure. The, likely recipient of the Lys53 proton is a water-His56 pair that serves to, relay the proton to the carbonyl oxygen of the phosphonoacetaldehyde, (Pald) substrate upon addition of the Lys53. The pH-rate profile analysis, of active-site mutants was carried out to test this proposal. The proximal, core domain residues Cys22 and Tyr128 were ruled out, and the role of cap, domain His56 was supported by the results. The X-ray crystallographic, structure of wild-type phosphonatase reduced with NaBH4 in the presence of, Pald was determined at 2.4A resolution to reveal N epsilon-ethyl-Lys53, juxtaposed with a sulfate ligand bound in the phosphate site. The position, of the C2 of the N-ethyl group in this structure is consistent with the, hypothesis that the cap domain N epsilon-ethylenamine-Lys53 functions as a, general base in the hydrolysis of the aspartylphosphate bi-covalent enzyme, intermediate. Because the enzyme residues proposed to play a key role in, P-C bond cleavage are localized on the cap domain, this domain appears to, have evolved to support the diversification of the HAD phosphatase core, domain for catalysis of hydrolytic P-C bond cleavage.

==About this Structure==
2IOF is a [http://en.wikipedia.org/wiki/Protein_complex Protein complex] structure of sequences from [http://en.wikipedia.org/wiki/Bacillus_cereus Bacillus cereus] with PO4 and MG as [http://en.wikipedia.org/wiki/ligands ligands]. Full crystallographic information is available from [http://ispc.weizmann.ac.il/oca-bin/ocashort?id=2IOF OCA]. 

==Reference==
Diversification of function in the haloacid dehalogenase enzyme superfamily: The role of the cap domain in hydrolytic phosphoruscarbon bond cleavage., Lahiri SD, Zhang G, Dunaway-Mariano D, Allen KN, Bioorg Chem. 2006 Dec;34(6):394-409. Epub 2006 Oct 27. PMID:[http://ispc.weizmann.ac.il//pmbin/getpm?pmid=17070898 17070898]
[[Category: Bacillus cereus]]
[[Category: Protein complex]]
[[Category: Allen, K.A.]]
[[Category: Dunaway-Mariano, D.]]
[[Category: Lahiri, S.D.]]
[[Category: Zhang, G.]]
[[Category: MG]]
[[Category: PO4]]
[[Category: haloacid dehalogenase superfamily]]
[[Category: phosphonoacetaldehyde hydrolase]]

''Page seeded by [http://ispc.weizmann.ac.il/oca OCA ] on Wed Nov 21 12:24:06 2007''