2aag

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

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

'''Crystal Structures of the Wild-type, Mutant-P1A and Inactivated Malonate Semialdehyde Decarboxylase: A Structural Basis for the Decarboxylase and Hydratase Activities'''<br />

==Overview==

Malonate semialdehyde decarboxylase (MSAD) from Pseudomonas pavonaceae 170, is a tautomerase superfamily member that converts malonate semialdehyde to, acetaldehyde by a mechanism utilizing Pro-1 and Arg-75. Pro-1 and Arg-75, have also been implicated in the hydratase activity of MSAD in which, 2-oxo-3-pentynoate is processed to acetopyruvate. Crystal structures of, MSAD (1.8 A resolution), the P1A mutant of MSAD (2.7 A resolution), and, MSAD inactivated by 3-chloropropiolate (1.6 A resolution), a, mechanism-based inhibitor activated by the hydratase activity of MSAD, have been determined. A comparison of the P1A-MSAD and MSAD structures, reveals little geometric alteration, indicating that Pro-1 plays an, important catalytic role but not a critical structural role. The, structures of wild-type MSAD and MSAD covalently modified at Pro-1 by, 3-oxopropanoate, the adduct resulting from the incubation of MSAD and, 3-chloropropiolate, implicate Asp-37 as the residue that activates a water, molecule for attack at C-3 of 3-chloropropiolate to initiate a Michael, addition of water. The interactions of Arg-73 and Arg-75 with the C-1, carboxylate group of the adduct suggest these residues polarize the, alpha,beta-unsaturated acid and facilitate the addition of water. On the, basis of these structures, a mechanism for the inactivation of MSAD by, 3-chloropropiolate can be formulated along with mechanisms for the, decarboxylase and hydratase activities. The results also provide, additional evidence supporting the hypothesis that MSAD and, trans-3-chloroacrylic acid dehalogenase, a tautomerase superfamily member, preceding MSAD in the trans-1,3-dichloropropene degradation pathway, diverged from a common ancestor but retained the key elements for the, conjugate addition of water.

 

==About this Structure==

2AAG is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Pseudomonas_pavonaceae Pseudomonas pavonaceae]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2AAG OCA].

 

==Reference==

Crystal structures of the wild-type, P1A mutant, and inactivated malonate semialdehyde decarboxylase: a structural basis for the decarboxylase and hydratase activities., Almrud JJ, Poelarends GJ, Johnson WH Jr, Serrano H, Hackert ML, Whitman CP, Biochemistry. 2005 Nov 15;44(45):14818-27. PMID:[http://ispc.weizmann.ac.il//pmbin/getpm?pmid=16274229 16274229]

[[Category: Almrud, J.J.]]

[[Category: Hackert, M.L.]]

[[Category: Jr., W.H.Johnson.]]

[[Category: Poelarends, G.J.]]

[[Category: Serrano, H.]]

[[Category: Whitman, C.P.]]