1Z7E

Crystal structure of full length ArnA

Summary for 1Z7E

• Entry DOI: 10.2210/pdb1z7e/pdb
• Related: 1Z73 1Z74 1Z75 1Z7B
• Descriptor: protein ArnA, ADENOSINE-5'-TRIPHOSPHATE, URIDINE-5'-DIPHOSPHATE-GLUCURONIC ACID (3 entities in total)
• Functional Keywords: rossmann fold; ob-like fold, hydrolase
• Biological source: Escherichia coli
• Total number of polymer chains: 6
• Total formula weight: 452839.43

Authors

Gatzeva-Topalova, P.Z.,May, A.P.,Sousa, M.C. (deposition date: 2005-03-24, release date: 2005-06-07, Last modification date: 2023-08-23)

Primary citation

Gatzeva-Topalova, P.Z.,May, A.P.,Sousa, M.C.
Structure and Mechanism of ArnA: Conformational Change Implies Ordered Dehydrogenase Mechanism in Key Enzyme for Polymyxin Resistance
Structure, 13:929-942, 2005

PubMed Abstract: 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.

PubMed: 15939024
DOI: 10.1016/j.str.2005.03.018

Experimental method

X-RAY DIFFRACTION (3 Å)