2aag: Difference between revisions

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

OverviewOverview

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 StructureAbout this Structure

2AAG is a Single protein structure of sequence from Pseudomonas pavonaceae. Full crystallographic information is available from OCA.

ReferenceReference

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:16274229

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 ==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.
+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==
@@ Line 13: / Line 13: @@
 [[Category: Pseudomonas pavonaceae]]
 [[Category: Single protein]]
-[[Category: Almrud, J.J.]]
+[[Category: Almrud, J J.]]
-[[Category: Hackert, M.L.]]
+[[Category: Hackert, M L.]]
-[[Category: Jr., W.H.Johnson.]]
+[[Category: Jr., W H.Johnson.]]
-[[Category: Poelarends, G.J.]]
+[[Category: Poelarends, G J.]]
 [[Category: Serrano, H.]]
-[[Category: Whitman, C.P.]]
+[[Category: Whitman, C P.]]
 [[Category: tautomerase superfamily; beta-alpha-beta; homotrimeric]]
-''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Tue Jan 29 17:58:08 2008''
+''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 16:25:28 2008''