Structural highlights
Function
ARGI_PLAF7 Catalyzes the hydrolysis of L-arginine into urea and L-ornithine, which is a precursor for polyamine biosynthesis (PubMed:15843155, PubMed:19456858, PubMed:20527960, PubMed:21728378). May play a role in parasite intra-hepatic development during the host liver stage (By similarity).[UniProtKB:A0A509AF89][1] [2] [3] [4]
Evolutionary Conservation
Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.
Publication Abstract from PubMed
The 2.15 A resolution crystal structure of arginase from Plasmodium falciparum, the parasite that causes cerebral malaria, is reported in complex with the boronic acid inhibitor 2(S)-amino-6-boronohexanoic acid (ABH) (K(d) = 11 muM). This is the first crystal structure of a parasitic arginase. Various protein constructs were explored to identify an optimally active enzyme form for inhibition and structural studies and to probe the structure and function of two polypeptide insertions unique to malarial arginase: a 74-residue low-complexity region contained in loop L2 and an 11-residue segment contained in loop L8. Structural studies indicate that the low-complexity region is largely disordered and is oriented away from the trimer interface; its deletion does not significantly compromise enzyme activity. The loop L8 insertion is located at the trimer interface and makes several intra- and intermolecular interactions important for enzyme function. In addition, we also demonstrate that arg- Plasmodium berghei sporozoites show significantly decreased liver infectivity in vivo. Therefore, inhibition of malarial arginase may serve as a possible candidate for antimalarial therapy against liver-stage infection, and ABH may serve as a lead for the development of inhibitors.
Crystal Structure of Arginase from Plasmodium falciparum and Implications for l-Arginine Depletion in Malarial Infection .,Dowling DP, Ilies M, Olszewski KL, Portugal S, Mota MM, Llinas M, Christianson DW Biochemistry. 2010 Jun 9. PMID:20527960[5]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Müller IB, Walter RD, Wrenger C. Structural metal dependency of the arginase from the human malaria parasite Plasmodium falciparum. Biol Chem. 2005 Feb;386(2):117-26. PMID:15843155 doi:10.1515/BC.2005.015
- ↑ Wells GA, Muller IB, Wrenger C, Louw AI. The activity of Plasmodium falciparum arginase is mediated by a novel inter-monomer salt-bridge between Glu295-Arg404. FEBS J. 2009 Jul;276(13):3517-30. Epub 2009 May 18. PMID:19456858 doi:10.1111/j.1742-4658.2009.07073.x
- ↑ Dowling DP, Ilies M, Olszewski KL, Portugal S, Mota MM, Llinas M, Christianson DW. Crystal Structure of Arginase from Plasmodium falciparum and Implications for l-Arginine Depletion in Malarial Infection . Biochemistry. 2010 Jun 9. PMID:20527960 doi:10.1021/bi100390z
- ↑ Ilies M, Di Costanzo L, Dowling DP, Thorn KJ, Christianson DW. Binding of alpha,alpha-Disubstituted Amino Acids to Arginase Suggests New Avenues for Inhibitor Design. J Med Chem. 2011 Jul 18. PMID:21728378 doi:10.1021/jm200443b
- ↑ Dowling DP, Ilies M, Olszewski KL, Portugal S, Mota MM, Llinas M, Christianson DW. Crystal Structure of Arginase from Plasmodium falciparum and Implications for l-Arginine Depletion in Malarial Infection . Biochemistry. 2010 Jun 9. PMID:20527960 doi:10.1021/bi100390z
