1z74
From Proteopedia
| Line 1: | Line 1: | ||
[[Image:1z74.gif|left|200px]] | [[Image:1z74.gif|left|200px]] | ||
| - | + | <!-- | |
| - | + | The line below this paragraph, containing "STRUCTURE_1z74", creates the "Structure Box" on the page. | |
| - | + | You may change the PDB parameter (which sets the PDB file loaded into the applet) | |
| - | + | or the SCENE parameter (which sets the initial scene displayed when the page is loaded), | |
| - | + | or leave the SCENE parameter empty for the default display. | |
| - | + | --> | |
| - | + | {{STRUCTURE_1z74| PDB=1z74 | SCENE= }} | |
| - | + | ||
| - | + | ||
| - | }} | + | |
'''Crystal Structure of E.coli ArnA dehydrogenase (decarboxylase) domain, R619Y mutant''' | '''Crystal Structure of E.coli ArnA dehydrogenase (decarboxylase) domain, R619Y mutant''' | ||
| Line 28: | Line 25: | ||
[[Category: May, A P.]] | [[Category: May, A P.]] | ||
[[Category: Sousa, M C.]] | [[Category: Sousa, M C.]] | ||
| - | [[Category: | + | [[Category: Rossmann fold]] |
| - | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sat May 3 17:15:40 2008'' | |
| - | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on | + | |
Revision as of 14:15, 3 May 2008
Crystal Structure of E.coli ArnA dehydrogenase (decarboxylase) domain, R619Y 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
1Z74 is a Single protein structure of sequence from Escherichia coli. 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 Page seeded by OCA on Sat May 3 17:15:40 2008
