1poj: Difference between revisions

Revision as of 15:30, 21 February 2008

Isoaspartyl Dipeptidase with bound inhibitor

OverviewOverview

L-aspartyl and L-asparaginyl residues in proteins spontaneously undergo intra-residue rearrangements forming isoaspartyl/beta-aspartyl residues linked through their side-chain beta-carboxyl group with the following amino acid. In order to avoid accumulation of isoaspartyl dipeptides left over from protein degradation, some bacteria have developed specialized isoaspartyl/beta-aspartyl zinc dipeptidases sequentially unrelated to other peptidases, which also poorly degrade alpha-aspartyl dipeptides. We have expressed and crystallized the 390 amino acid residue isoaspartyl dipeptidase (IadA) from E.coli, and have determined its crystal structure in the absence and presence of the phosphinic inhibitor Asp-Psi[PO(2)CH(2)]-LeuOH. This structure reveals an octameric particle of 422 symmetry, with each polypeptide chain organized in a (alphabeta)(8) TIM-like barrel catalytic domain attached to a U-shaped beta-sandwich domain. At the C termini of the beta-strands of the beta-barrel, the two catalytic zinc ions are surrounded by four His, a bridging carbamylated Lys and an Asp residue, which seems to act as a proton shuttle. A large beta-hairpin loop protruding from the (alphabeta)(8) barrel is disordered in the free peptidase, but forms a flap that stoppers the barrel entrance to the active center upon binding of the dipeptide mimic. This isoaspartyl dipeptidase shows strong topological homology with the alpha-subunit of the binickel-containing ureases, the dinuclear zinc dihydroorotases, hydantoinases and phosphotriesterases, and the mononuclear adenosine and cytosine deaminases, which all are catalyzing hydrolytic reactions at carbon or phosphorous centers. Thus, nature has adapted an existing fold with catalytic tools suitable for hydrolysis of amide bonds to the binding requirements of a peptidase.

About this StructureAbout this Structure

1POJ is a Single protein structure of sequence from Escherichia coli with and as ligands. Full crystallographic information is available from OCA.

ReferenceReference

X-ray structure of isoaspartyl dipeptidase from E.coli: a dinuclear zinc peptidase evolved from amidohydrolases., Jozic D, Kaiser JT, Huber R, Bode W, Maskos K, J Mol Biol. 2003 Sep 5;332(1):243-56. PMID:12946361

Page seeded by OCA on Thu Feb 21 14:30:51 2008

Proteopedia Page Contributors and Editors (what is this?)Proteopedia Page Contributors and Editors (what is this?)

OCA

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-[[Image:1poj.jpg|left|200px]]<br /><applet load="1poj" size="450" color="white" frame="true" align="right" spinBox="true"
+[[Image:1poj.jpg|left|200px]]<br /><applet load="1poj" size="350" color="white" frame="true" align="right" spinBox="true"
 caption="1poj, resolution 3.3&Aring;" />
 '''Isoaspartyl Dipeptidase with bound inhibitor'''<br />
 ==Overview==
-L-aspartyl and L-asparaginyl residues in proteins spontaneously undergo, intra-residue rearrangements forming isoaspartyl/beta-aspartyl residues, linked through their side-chain beta-carboxyl group with the following, amino acid. In order to avoid accumulation of isoaspartyl dipeptides left, over from protein degradation, some bacteria have developed specialized, isoaspartyl/beta-aspartyl zinc dipeptidases sequentially unrelated to, other peptidases, which also poorly degrade alpha-aspartyl dipeptides. We, have expressed and crystallized the 390 amino acid residue isoaspartyl, dipeptidase (IadA) from E.coli, and have determined its crystal structure, in the absence and presence of the phosphinic inhibitor, Asp-Psi[PO(2)CH(2)]-LeuOH. This structure reveals an octameric particle of, 422 symmetry, with each polypeptide chain organized in a (alphabeta)(8), TIM-like barrel catalytic domain attached to a U-shaped beta-sandwich, domain. At the C termini of the beta-strands of the beta-barrel, the two, catalytic zinc ions are surrounded by four His, a bridging carbamylated, Lys and an Asp residue, which seems to act as a proton shuttle. A large, beta-hairpin loop protruding from the (alphabeta)(8) barrel is disordered, in the free peptidase, but forms a flap that stoppers the barrel entrance, to the active center upon binding of the dipeptide mimic. This isoaspartyl, dipeptidase shows strong topological homology with the alpha-subunit of, the binickel-containing ureases, the dinuclear zinc dihydroorotases, hydantoinases and phosphotriesterases, and the mononuclear adenosine and, cytosine deaminases, which all are catalyzing hydrolytic reactions at, carbon or phosphorous centers. Thus, nature has adapted an existing fold, with catalytic tools suitable for hydrolysis of amide bonds to the binding, requirements of a peptidase.
+L-aspartyl and L-asparaginyl residues in proteins spontaneously undergo intra-residue rearrangements forming isoaspartyl/beta-aspartyl residues linked through their side-chain beta-carboxyl group with the following amino acid. In order to avoid accumulation of isoaspartyl dipeptides left over from protein degradation, some bacteria have developed specialized isoaspartyl/beta-aspartyl zinc dipeptidases sequentially unrelated to other peptidases, which also poorly degrade alpha-aspartyl dipeptides. We have expressed and crystallized the 390 amino acid residue isoaspartyl dipeptidase (IadA) from E.coli, and have determined its crystal structure in the absence and presence of the phosphinic inhibitor Asp-Psi[PO(2)CH(2)]-LeuOH. This structure reveals an octameric particle of 422 symmetry, with each polypeptide chain organized in a (alphabeta)(8) TIM-like barrel catalytic domain attached to a U-shaped beta-sandwich domain. At the C termini of the beta-strands of the beta-barrel, the two catalytic zinc ions are surrounded by four His, a bridging carbamylated Lys and an Asp residue, which seems to act as a proton shuttle. A large beta-hairpin loop protruding from the (alphabeta)(8) barrel is disordered in the free peptidase, but forms a flap that stoppers the barrel entrance to the active center upon binding of the dipeptide mimic. This isoaspartyl dipeptidase shows strong topological homology with the alpha-subunit of the binickel-containing ureases, the dinuclear zinc dihydroorotases, hydantoinases and phosphotriesterases, and the mononuclear adenosine and cytosine deaminases, which all are catalyzing hydrolytic reactions at carbon or phosphorous centers. Thus, nature has adapted an existing fold with catalytic tools suitable for hydrolysis of amide bonds to the binding requirements of a peptidase.
 ==About this Structure==
-POJ is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Escherichia_coli Escherichia coli] with ZN and AE1 as [http://en.wikipedia.org/wiki/ligands ligands]. Full crystallographic information is available from [http://ispc.weizmann.ac.il/oca-bin/ocashort?id=1POJ OCA].
+POJ is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Escherichia_coli Escherichia coli] with <scene name='pdbligand=ZN:'>ZN</scene> and <scene name='pdbligand=AE1:'>AE1</scene> as [http://en.wikipedia.org/wiki/ligands ligands]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1POJ OCA].
 ==Reference==
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 [[Category: Huber, R.]]
 [[Category: Jozic, D.]]
-[[Category: Kaiser, J.T.]]
+[[Category: Kaiser, J T.]]
 [[Category: Maskos, K.]]
 [[Category: AE1]]
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 [[Category: hydrolase]]
-''Page seeded by [http://ispc.weizmann.ac.il/oca OCA ] on Tue Nov 20 23:58:29 2007''
+''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 14:30:51 2008''