1c24: Difference between revisions

Revision as of 13:01, 21 February 2008

E. COLI METHIONINE AMINOPEPTIDASE: METHIONINE PHOSPHINATE COMPLEX

OverviewOverview

In an effort to differentiate between alternative mechanistic schemes that have been postulated for Escherichia coli methionine aminopeptidase (eMetAP), the modes of binding of a series of products and phosphorus-based transition-state analogues were determined by X-ray crystallography. Methionine phosphonate, norleucine phosphonate, and methionine phosphinate bind with the N-terminal group interacting with Co2 and with the respective phosphorus oxygens binding between the metals, interacting in a bifurcated manner with Co1 and His178 and hydrogen bonded to His79. In contrast, the reaction product methionine and its analogue trifluoromethionine lose interactions with Co1 and His79. The interactions with the transition-state analogues are, in general, very similar to those seen previously for the complex of the enzyme with a bestatin-based inhibitor. The mode of interaction of His79 is, however, different. In the case of the bestatin-based inhibitor, His79 interacts with atoms in the peptide bond between the P(1)' and P(2)' residues. In the present transition-state analogues, however, the histidine moves 1.2 A toward the metal center and hydrogen bonds with the atom that corresponds to the nitrogen of the scissile peptide bond (i.e., between the P(1) and P(1)' residues). These observations tend to support one of the mechanistic schemes for eMetAP considered before, although with a revision in the role played by His79. The results also suggest parallels between the mechanism of action of methionine aminopeptidase and other "pita-bread" enzymes including aminopeptidase P and creatinase.

About this StructureAbout this Structure

1C24 is a Single protein structure of sequence from Escherichia coli with , and as ligands. Active as Methionyl aminopeptidase, with EC number 3.4.11.18 Full crystallographic information is available from OCA.

ReferenceReference

Insights into the mechanism of Escherichia coli methionine aminopeptidase from the structural analysis of reaction products and phosphorus-based transition-state analogues., Lowther WT, Zhang Y, Sampson PB, Honek JF, Matthews BW, Biochemistry. 1999 Nov 9;38(45):14810-9. PMID:10555963

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-[[Image:1c24.gif|left|200px]]<br /><applet load="1c24" size="450" color="white" frame="true" align="right" spinBox="true"
+[[Image:1c24.gif|left|200px]]<br /><applet load="1c24" size="350" color="white" frame="true" align="right" spinBox="true"
 caption="1c24, resolution 1.70&Aring;" />
 '''E. COLI METHIONINE AMINOPEPTIDASE: METHIONINE PHOSPHINATE COMPLEX'''<br />
 ==Overview==
-In an effort to differentiate between alternative mechanistic schemes that, have been postulated for Escherichia coli methionine aminopeptidase, (eMetAP), the modes of binding of a series of products and, phosphorus-based transition-state analogues were determined by X-ray, crystallography. Methionine phosphonate, norleucine phosphonate, and, methionine phosphinate bind with the N-terminal group interacting with Co2, and with the respective phosphorus oxygens binding between the metals, interacting in a bifurcated manner with Co1 and His178 and hydrogen bonded, to His79. In contrast, the reaction product methionine and its analogue, trifluoromethionine lose interactions with Co1 and His79. The interactions, with the transition-state analogues are, in general, very similar to those, seen previously for the complex of the enzyme with a bestatin-based, inhibitor. The mode of interaction of His79 is, however, different. In the, case of the bestatin-based inhibitor, His79 interacts with atoms in the, peptide bond between the P(1)' and P(2)' residues. In the present, transition-state analogues, however, the histidine moves 1.2 A toward the, metal center and hydrogen bonds with the atom that corresponds to the, nitrogen of the scissile peptide bond (i.e., between the P(1) and P(1)', residues). These observations tend to support one of the mechanistic, schemes for eMetAP considered before, although with a revision in the role, played by His79. The results also suggest parallels between the mechanism, of action of methionine aminopeptidase and other "pita-bread" enzymes, including aminopeptidase P and creatinase.
+In an effort to differentiate between alternative mechanistic schemes that have been postulated for Escherichia coli methionine aminopeptidase (eMetAP), the modes of binding of a series of products and phosphorus-based transition-state analogues were determined by X-ray crystallography. Methionine phosphonate, norleucine phosphonate, and methionine phosphinate bind with the N-terminal group interacting with Co2 and with the respective phosphorus oxygens binding between the metals, interacting in a bifurcated manner with Co1 and His178 and hydrogen bonded to His79. In contrast, the reaction product methionine and its analogue trifluoromethionine lose interactions with Co1 and His79. The interactions with the transition-state analogues are, in general, very similar to those seen previously for the complex of the enzyme with a bestatin-based inhibitor. The mode of interaction of His79 is, however, different. In the case of the bestatin-based inhibitor, His79 interacts with atoms in the peptide bond between the P(1)' and P(2)' residues. In the present transition-state analogues, however, the histidine moves 1.2 A toward the metal center and hydrogen bonds with the atom that corresponds to the nitrogen of the scissile peptide bond (i.e., between the P(1) and P(1)' residues). These observations tend to support one of the mechanistic schemes for eMetAP considered before, although with a revision in the role played by His79. The results also suggest parallels between the mechanism of action of methionine aminopeptidase and other "pita-bread" enzymes including aminopeptidase P and creatinase.
 ==About this Structure==
-C24 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 CO, NA and MPJ as [http://en.wikipedia.org/wiki/ligands ligands]. Active as [http://en.wikipedia.org/wiki/Methionyl_aminopeptidase Methionyl aminopeptidase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.4.11.18 3.4.11.18] Full crystallographic information is available from [http://ispc.weizmann.ac.il/oca-bin/ocashort?id=1C24 OCA].
+C24 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=CO:'>CO</scene>, <scene name='pdbligand=NA:'>NA</scene> and <scene name='pdbligand=MPJ:'>MPJ</scene> as [http://en.wikipedia.org/wiki/ligands ligands]. Active as [http://en.wikipedia.org/wiki/Methionyl_aminopeptidase Methionyl aminopeptidase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.4.11.18 3.4.11.18] Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1C24 OCA].
 ==Reference==
@@ Line 14: / Line 14: @@
 [[Category: Methionyl aminopeptidase]]
 [[Category: Single protein]]
-[[Category: Honek, J.F.]]
+[[Category: Honek, J F.]]
-[[Category: Lowther, W.T.]]
+[[Category: Lowther, W T.]]
-[[Category: Matthews, B.W.]]
+[[Category: Matthews, B W.]]
-[[Category: Sampson, P.B.]]
+[[Category: Sampson, P B.]]
 [[Category: Zhang, Y.]]
 [[Category: CO]]
@@ Line 25: / Line 25: @@
 [[Category: product complex]]
-''Page seeded by [http://ispc.weizmann.ac.il/oca OCA ] on Tue Nov 20 12:05:49 2007''
+''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 12:01:34 2008''