1q54
From Proteopedia
(New page: 200px<br /><applet load="1q54" size="450" color="white" frame="true" align="right" spinBox="true" caption="1q54, resolution 1.93Å" /> '''STRUCTURE AND MECHAN...) |
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caption="1q54, resolution 1.93Å" /> | caption="1q54, resolution 1.93Å" /> | ||
'''STRUCTURE AND MECHANISM OF ACTION OF ISOPENTENYLPYROPHOSPHATE-DIMETHYLALLYLPYROPHOSPHATE ISOMERASE: COMPLEX WITH THE BROMOHYDRINE OF IPP'''<br /> | '''STRUCTURE AND MECHANISM OF ACTION OF ISOPENTENYLPYROPHOSPHATE-DIMETHYLALLYLPYROPHOSPHATE ISOMERASE: COMPLEX WITH THE BROMOHYDRINE OF IPP'''<br /> | ||
==Overview== | ==Overview== | ||
| - | We have obtained the three-dimensional X-ray crystallographic structure of a C67A mutant Escherichia coli isopentenylpyrophosphate-dimethylallylpyrophosphate isomerase (EC 5.3.3.2) complexed with the bromohydrin of isopentenylpyrophosphate, at 1.93 | + | We have obtained the three-dimensional X-ray crystallographic structure of a C67A mutant Escherichia coli isopentenylpyrophosphate-dimethylallylpyrophosphate isomerase (EC 5.3.3.2) complexed with the bromohydrin of isopentenylpyrophosphate, at 1.93 A resolution. The overall backbone fold is very similar to that obtained previously for the wild-type enzyme in the presence of a divalent metal cation (Mn2+ or Mg2+). However, in the new structure, there are two metal binding sites, not just one. The first metal binding site is occupied by Mn2+, coordinated to three histidine and two glutamate residues, while the second is occupied by Mg2+, coordinated to two bromohydrin-ligand phosphate oxygens, the carbonyl oxygen of A67, a carboxyl oxygen of E87, and two water molecules. The C3 hydroxyl group of the bromohydrin inhibitor is involved in a short hydrogen bond to the carboxyl group of E116, one of the two Mn-bound glutamates. The structure obtained is consistent with a mechanism of action of the enzyme in which the carboxyl group of E116 protonates the double bond in isopentenylpyrophosphate, forming a carbocation, followed by removal of a C2 proton by the thiolate of C67, in the wild-type enzyme. The inhibition of the enzyme by a wide variety of other potent inhibitors is also readily explained on the basis of the bromohydrin inhibitor structure. |
==About this Structure== | ==About this Structure== | ||
| - | 1Q54 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 MN, MG and BHI as [http://en.wikipedia.org/wiki/ligands ligands]. This structure | + | 1Q54 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=MN:'>MN</scene>, <scene name='pdbligand=MG:'>MG</scene> and <scene name='pdbligand=BHI:'>BHI</scene> as [http://en.wikipedia.org/wiki/ligands ligands]. This structure supersedes the now removed PDB entry 1N2U. Active as [http://en.wikipedia.org/wiki/Isopentenyl-diphosphate_Delta-isomerase Isopentenyl-diphosphate Delta-isomerase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=5.3.3.2 5.3.3.2] Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1Q54 OCA]. |
==Reference== | ==Reference== | ||
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[[Category: complex]] | [[Category: complex]] | ||
| - | ''Page seeded by [http:// | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 14:35:55 2008'' |
Revision as of 12:35, 21 February 2008
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STRUCTURE AND MECHANISM OF ACTION OF ISOPENTENYLPYROPHOSPHATE-DIMETHYLALLYLPYROPHOSPHATE ISOMERASE: COMPLEX WITH THE BROMOHYDRINE OF IPP
Overview
We have obtained the three-dimensional X-ray crystallographic structure of a C67A mutant Escherichia coli isopentenylpyrophosphate-dimethylallylpyrophosphate isomerase (EC 5.3.3.2) complexed with the bromohydrin of isopentenylpyrophosphate, at 1.93 A resolution. The overall backbone fold is very similar to that obtained previously for the wild-type enzyme in the presence of a divalent metal cation (Mn2+ or Mg2+). However, in the new structure, there are two metal binding sites, not just one. The first metal binding site is occupied by Mn2+, coordinated to three histidine and two glutamate residues, while the second is occupied by Mg2+, coordinated to two bromohydrin-ligand phosphate oxygens, the carbonyl oxygen of A67, a carboxyl oxygen of E87, and two water molecules. The C3 hydroxyl group of the bromohydrin inhibitor is involved in a short hydrogen bond to the carboxyl group of E116, one of the two Mn-bound glutamates. The structure obtained is consistent with a mechanism of action of the enzyme in which the carboxyl group of E116 protonates the double bond in isopentenylpyrophosphate, forming a carbocation, followed by removal of a C2 proton by the thiolate of C67, in the wild-type enzyme. The inhibition of the enzyme by a wide variety of other potent inhibitors is also readily explained on the basis of the bromohydrin inhibitor structure.
About this Structure
1Q54 is a Single protein structure of sequence from Escherichia coli with , and as ligands. This structure supersedes the now removed PDB entry 1N2U. Active as Isopentenyl-diphosphate Delta-isomerase, with EC number 5.3.3.2 Full crystallographic information is available from OCA.
Reference
Structure and mechanism of action of isopentenylpyrophosphate-dimethylallylpyrophosphate isomerase., Wouters J, Oudjama Y, Ghosh S, Stalon V, Droogmans L, Oldfield E, J Am Chem Soc. 2003 Mar 19;125(11):3198-9. PMID:12630859
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