1z7b: Difference between revisions
New page: left|200px<br /><applet load="1z7b" size="450" color="white" frame="true" align="right" spinBox="true" caption="1z7b, resolution 2.31Å" /> '''Crystal structure of... |
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[[Image:1z7b.gif|left|200px]]<br /><applet load="1z7b" size=" | [[Image:1z7b.gif|left|200px]]<br /><applet load="1z7b" size="350" color="white" frame="true" align="right" spinBox="true" | ||
caption="1z7b, resolution 2.31Å" /> | caption="1z7b, resolution 2.31Å" /> | ||
'''Crystal structure of E.coli ArnA dehydrogenase (decarboxylase) domain, R619E mutant'''<br /> | '''Crystal structure of E.coli ArnA dehydrogenase (decarboxylase) domain, R619E mutant'''<br /> | ||
==Overview== | ==Overview== | ||
The modification of lipid A with 4-amino-4-deoxy-L-arabinose (Ara4N) | The modification of lipid A with 4-amino-4-deoxy-L-arabinose (Ara4N) allows gram-negative bacteria to resist the antimicrobial activity of cationic antimicrobial peptides and antibiotics such as polymyxin. ArnA is the first enzyme specific to the lipid A-Ara4N pathway. It contains two functionally and physically separable domains: a dehydrogenase domain (ArnA_DH) catalyzing the NAD+-dependent oxidative decarboxylation of UDP-Glucuronic acid (UDP-GlcA), and a transformylase domain that formylates UDP-Ara4N. Here, we describe the crystal structure of the full-length bifunctional ArnA with UDP-GlcA and ATP bound to the dehydrogenase domain. Binding of UDP-GlcA triggers a 17 A conformational change in ArnA_DH that opens the NAD+ binding site while trapping UDP-GlcA. We propose an ordered mechanism of substrate binding and product release. Mutation of residues R619 and S433 demonstrates their importance in catalysis and suggests that R619 functions as a general acid in catalysis. The proposed mechanism for ArnA_DH has important implications for the design of selective inhibitors. | ||
==About this Structure== | ==About this Structure== | ||
1Z7B 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 SO4 as [http://en.wikipedia.org/wiki/ligand ligand]. Full crystallographic information is available from [http:// | 1Z7B 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=SO4:'>SO4</scene> as [http://en.wikipedia.org/wiki/ligand ligand]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1Z7B OCA]. | ||
==Reference== | ==Reference== | ||
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[[Category: Escherichia coli]] | [[Category: Escherichia coli]] | ||
[[Category: Single protein]] | [[Category: Single protein]] | ||
[[Category: Gatzeva-Topalova, P | [[Category: Gatzeva-Topalova, P Z.]] | ||
[[Category: May, A | [[Category: May, A P.]] | ||
[[Category: Sousa, M | [[Category: Sousa, M C.]] | ||
[[Category: SO4]] | [[Category: SO4]] | ||
[[Category: rossmann fold]] | [[Category: rossmann fold]] | ||
''Page seeded by [http:// | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 16:12:47 2008'' | ||
Revision as of 14:12, 21 February 2008
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Crystal structure of E.coli ArnA dehydrogenase (decarboxylase) domain, R619E mutant
Overview
The modification of lipid A with 4-amino-4-deoxy-L-arabinose (Ara4N) allows gram-negative bacteria to resist the antimicrobial activity of cationic antimicrobial peptides and antibiotics such as polymyxin. ArnA is the first enzyme specific to the lipid A-Ara4N pathway. It contains two functionally and physically separable domains: a dehydrogenase domain (ArnA_DH) catalyzing the NAD+-dependent oxidative decarboxylation of UDP-Glucuronic acid (UDP-GlcA), and a transformylase domain that formylates UDP-Ara4N. Here, we describe the crystal structure of the full-length bifunctional ArnA with UDP-GlcA and ATP bound to the dehydrogenase domain. Binding of UDP-GlcA triggers a 17 A conformational change in ArnA_DH that opens the NAD+ binding site while trapping UDP-GlcA. We propose an ordered mechanism of substrate binding and product release. Mutation of residues R619 and S433 demonstrates their importance in catalysis and suggests that R619 functions as a general acid in catalysis. The proposed mechanism for ArnA_DH has important implications for the design of selective inhibitors.
About this Structure
1Z7B is a Single protein structure of sequence from Escherichia coli with SO4 as ligand. Full crystallographic information is available from OCA.
Reference
Structure and mechanism of ArnA: conformational change implies ordered dehydrogenase mechanism in key enzyme for polymyxin resistance., Gatzeva-Topalova PZ, May AP, Sousa MC, Structure. 2005 Jun;13(6):929-42. PMID:15939024
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