2ies
From Proteopedia
(New page: 200px<br /><applet load="2ies" size="450" color="white" frame="true" align="right" spinBox="true" caption="2ies, resolution 3.10Å" /> '''Crystal Structure of...) |
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| - | [[Image:2ies.gif|left|200px]]<br /><applet load="2ies" size=" | + | [[Image:2ies.gif|left|200px]]<br /><applet load="2ies" size="350" color="white" frame="true" align="right" spinBox="true" |
caption="2ies, resolution 3.10Å" /> | caption="2ies, resolution 3.10Å" /> | ||
'''Crystal Structure of Aquifex aeolicus LpxC Complexed with Pyrophosphate'''<br /> | '''Crystal Structure of Aquifex aeolicus LpxC Complexed with Pyrophosphate'''<br /> | ||
==Overview== | ==Overview== | ||
| - | LpxC is a zinc metalloenzyme that catalyzes the first committed step in | + | LpxC is a zinc metalloenzyme that catalyzes the first committed step in the biosynthesis of lipid A, a vital component of the outer membrane of Gram-negative bacteria. Accordingly, the inhibition of LpxC is an attractive strategy for the treatment of Gram-negative bacterial infections. Here, we report the 2.7 A resolution X-ray crystal structure of LpxC from Aquifex aeolicus complexed with uridine 5'-diphosphate (UDP), and the 3.1 A resolution structure of LpxC complexed with pyrophosphate. The X-ray crystal structure of the LpxC-UDP complex provides the first view of interactions likely to be exploited by the substrate UDP group in the "basic patch" of the active site. The diphosphate group of UDP makes hydrogen bond interactions with strictly conserved residue K239 as well as solvent molecules. The ribose moiety of UDP interacts with partially conserved residue E197. The UDP uracil group hydrogen bonds with both the backbone NH group and the backbone carbonyl group of E160, and with the backbone NH group of K162 through an intervening water molecule. Finally, the alpha-phosphate and uracil groups of UDP interact with R143 and R262 through intervening water molecules. The structure of LpxC complexed with pyrophosphate reveals generally similar intermolecular interactions in the basic patch. Unexpectedly, diphosphate binding in both complexes is accompanied by coordination to an additional zinc ion, resulting in the identification of a new metal-binding site termed the E-site. The structures of the LpxC-UDP and LpxC-pyrophosphate complexes provide new insights with regard to substrate recognition in the basic patch and metal ion coordination in the active site of LpxC. |
==About this Structure== | ==About this Structure== | ||
| - | 2IES is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Aquifex_aeolicus Aquifex aeolicus] with ZN, CL, POP and PLM as [http://en.wikipedia.org/wiki/ligands ligands]. Full crystallographic information is available from [http:// | + | 2IES is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Aquifex_aeolicus Aquifex aeolicus] with <scene name='pdbligand=ZN:'>ZN</scene>, <scene name='pdbligand=CL:'>CL</scene>, <scene name='pdbligand=POP:'>POP</scene> and <scene name='pdbligand=PLM:'>PLM</scene> as [http://en.wikipedia.org/wiki/ligands ligands]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2IES OCA]. |
==Reference== | ==Reference== | ||
| - | Binding of | + | Binding of uridine 5'-diphosphate in the "basic patch" of the zinc deacetylase LpxC and implications for substrate binding., Gennadios HA, Christianson DW, Biochemistry. 2006 Dec 26;45(51):15216-23. Epub 2006 Nov 30. PMID:[http://ispc.weizmann.ac.il//pmbin/getpm?pmid=17176043 17176043] |
[[Category: Aquifex aeolicus]] | [[Category: Aquifex aeolicus]] | ||
[[Category: Single protein]] | [[Category: Single protein]] | ||
| - | [[Category: Christianson, D | + | [[Category: Christianson, D W.]] |
| - | [[Category: Gennadios, H | + | [[Category: Gennadios, H A.]] |
[[Category: CL]] | [[Category: CL]] | ||
[[Category: PLM]] | [[Category: PLM]] | ||
| Line 21: | Line 21: | ||
[[Category: alpha + beta fold]] | [[Category: alpha + beta fold]] | ||
| - | ''Page seeded by [http:// | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 17:52:03 2008'' |
Revision as of 15:52, 21 February 2008
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Crystal Structure of Aquifex aeolicus LpxC Complexed with Pyrophosphate
Overview
LpxC is a zinc metalloenzyme that catalyzes the first committed step in the biosynthesis of lipid A, a vital component of the outer membrane of Gram-negative bacteria. Accordingly, the inhibition of LpxC is an attractive strategy for the treatment of Gram-negative bacterial infections. Here, we report the 2.7 A resolution X-ray crystal structure of LpxC from Aquifex aeolicus complexed with uridine 5'-diphosphate (UDP), and the 3.1 A resolution structure of LpxC complexed with pyrophosphate. The X-ray crystal structure of the LpxC-UDP complex provides the first view of interactions likely to be exploited by the substrate UDP group in the "basic patch" of the active site. The diphosphate group of UDP makes hydrogen bond interactions with strictly conserved residue K239 as well as solvent molecules. The ribose moiety of UDP interacts with partially conserved residue E197. The UDP uracil group hydrogen bonds with both the backbone NH group and the backbone carbonyl group of E160, and with the backbone NH group of K162 through an intervening water molecule. Finally, the alpha-phosphate and uracil groups of UDP interact with R143 and R262 through intervening water molecules. The structure of LpxC complexed with pyrophosphate reveals generally similar intermolecular interactions in the basic patch. Unexpectedly, diphosphate binding in both complexes is accompanied by coordination to an additional zinc ion, resulting in the identification of a new metal-binding site termed the E-site. The structures of the LpxC-UDP and LpxC-pyrophosphate complexes provide new insights with regard to substrate recognition in the basic patch and metal ion coordination in the active site of LpxC.
About this Structure
2IES is a Single protein structure of sequence from Aquifex aeolicus with , , and as ligands. Full crystallographic information is available from OCA.
Reference
Binding of uridine 5'-diphosphate in the "basic patch" of the zinc deacetylase LpxC and implications for substrate binding., Gennadios HA, Christianson DW, Biochemistry. 2006 Dec 26;45(51):15216-23. Epub 2006 Nov 30. PMID:17176043
Page seeded by OCA on Thu Feb 21 17:52:03 2008
Categories: Aquifex aeolicus | Single protein | Christianson, D W. | Gennadios, H A. | CL | PLM | POP | ZN | Alpha + beta fold
