3HVM
Agmatine Deiminase from Helicobacter pylori
Summary for 3HVM
| Entry DOI | 10.2210/pdb3hvm/pdb |
| Descriptor | AGMATINE DEIMINASE (2 entities in total) |
| Functional Keywords | agmatine deiminase, hydrolase |
| Biological source | Helicobacter pylori |
| Total number of polymer chains | 1 |
| Total formula weight | 37614.13 |
| Authors | Jones, J.,Lovelace, L.,Lebioda, L.,Thompson, P. (deposition date: 2009-06-16, release date: 2010-01-19, Last modification date: 2023-09-06) |
| Primary citation | Jones, J.E.,Causey, C.P.,Lovelace, L.,Knuckley, B.,Flick, H.,Lebioda, L.,Thompson, P.R. Characterization and inactivation of an agmatine deiminase from Helicobacter pylori. Bioorg.Chem., 38:62-73, 2010 Cited by PubMed Abstract: Helicobacter pylori encodes a potential virulence factor, agmatine deiminase (HpAgD), which catalyzes the conversion of agmatine to N-carbamoyl putrescine (NCP) and ammonia - agmatine is decarboxylated arginine. Agmatine is an endogenous human cell signaling molecule that triggers the innate immune response in humans. Unlike H. pylori, humans do not encode an AgD; it is hypothesized that inhibition of this enzyme would increase the levels of agmatine, and thereby enhance the innate immune response. Taken together, these facts suggest that HpAgD is a potential drug target. Herein we describe the optimized expression, isolation, and purification of HpAgD (10-30 mg/L media). The initial kinetic characterization of this enzyme has also been performed. Additionally, the crystal structure of wild-type HpAgD has been determined at 2.1A resolution. This structure provides a molecular basis for the preferential deimination of agmatine, and identifies Asp198 as a key residue responsible for agmatine recognition, which has been confirmed experimentally. Information gathered from these studies led to the development and characterization of a novel class of haloacetamidine-based HpAgD inactivators. These compounds are the most potent AgD inhibitors ever described. PubMed: 20036411DOI: 10.1016/j.bioorg.2009.11.004 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (2.1 Å) |
Structure validation
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