Literature summary for 3.5.3.1 extracted from

Dowling, D.P.; Ilies, M.; Olszewski, K.L.; Portugal, S.; Mota, M.M.; Llinas, M.; Christianson, D.W.
Crystal structure of arginase from Plasmodium falciparum and implications for L-arginine depletion in malarial infection (2010), Biochemistry, 49, 5600-5608.

Application

Application	Comment	Organism
medicine	comparison of the infectivity of arg- and wild-type Plasmodium berghei by inoculation of mice using sporozoites dissected from mosquito salivary glands shows a significant reduction in infectivity in the arg- strain 40 h postinfection	Plasmodium berghei

Crystallization (Commentary)

Crystallization (Comment)	Organism
in complex with the boronic acid inhibitor 2(S)-amino-6-boronohexanoic acid, to 2.15 A resolution. There are 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	Plasmodium falciparum 3D7

Crystallization (Comment)

Organism

in complex with the boronic acid inhibitor 2(S)-amino-6-boronohexanoic acid, to 2.15 A resolution. There are 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

Plasmodium falciparum 3D7

Protein Variants

Protein Variants	Comment	Organism
additional information	construction of a N-terminal truncation beginning with K22 and bearing an N-terminal His-tag, i.e. dN-PFA, a similar N-terminal truncation with residues N84-D157 of loop L2 deleted, i.e. dN-PFA-L2S, mutant dN-PFA-H381A, and the dN-PFA-L8 chimera in which loop L8 is replaced with the shorter human arginase I sequence, and analysis of kinetic parameters	Plasmodium falciparum 3D7

Inhibitors

Inhibitors	Comment	Organism	Structure
2(S)-amino-6-boronohexanoic acid	-	Plasmodium falciparum 3D7

KM Value [mM]

KM Value [mM]	KM Value Maximum [mM]	Substrate	Comment	Organism
3.3	-	L-arginine	mutant dN-PFA, pH 8.5, 37°C	Plasmodium falciparum 3D7
4	-	L-arginine	mutant dN-PFA, pH 8.0, 37°C	Plasmodium falciparum 3D7
4	-	L-arginine	mutant dN-PFA-L2S, pH 8.0, 37°C	Plasmodium falciparum 3D7
10	-	L-arginine	mutant dN-PFA-H381A, pH 8.0, 37°C	Plasmodium falciparum 3D7
12	-	L-arginine	mutant dN-PFA-C6H, pH 8.0, 37°C	Plasmodium falciparum 3D7
20	-	L-arginine	mutant dN-PFA-L8, pH 8.0, 37°C	Plasmodium falciparum 3D7
25	-	L-arginine	mutant dN-PFA, pH 7.4, 37°C	Plasmodium falciparum 3D7

Organism

Organism	UniProt	Comment	Textmining
Plasmodium berghei	-	-	-
Plasmodium falciparum 3D7	Q8I384	-	-

Source Tissue

Source Tissue	Comment	Organism	Textmining

Substrates and Products (Substrate)

Substrates	Comment Substrates	Organism	Products	Comment (Products)	Rev.	Reac.
L-arginine + H2O	-	Plasmodium berghei	L-ornithine + urea	-	?
L-arginine + H2O	-	Plasmodium falciparum 3D7	L-ornithine + urea	-	?

Turnover Number [1/s]

Turnover Number Minimum [1/s]	Turnover Number Maximum [1/s]	Substrate	Comment	Organism
2	8	L-arginine	mutant dN-PFA-H381A, pH 8.0, 37°C	Plasmodium falciparum 3D7
76	-	L-arginine	mutant dN-PFA-C6H, pH 8.0, 37°C	Plasmodium falciparum 3D7
77	-	L-arginine	mutant dN-PFA, pH 7.4, 37°C	Plasmodium falciparum 3D7
320	-	L-arginine	mutant dN-PFA, pH 8.0, 37°C	Plasmodium falciparum 3D7
440	-	L-arginine	mutant dN-PFA, pH 8.5, 37°C	Plasmodium falciparum 3D7

Ki Value [mM]

Ki Value [mM]	Ki Value maximum [mM]	Inhibitor	Comment	Organism
0.01	-	2(S)-amino-6-boronohexanoic acid	mutant dN-PFA, pH 8.5, 37°C	Plasmodium falciparum 3D7
0.011	-	2(S)-amino-6-boronohexanoic acid	mutant dN-PFA, pH 7.4, 37°C	Plasmodium falciparum 3D7
0.012	-	2(S)-amino-6-boronohexanoic acid	mutant dN-PFA, pH 8.0, 37°C	Plasmodium falciparum 3D7
0.053	-	2(S)-amino-6-boronohexanoic acid	mutant dN-PFA-H381A, pH 8.0, 37°C	Plasmodium falciparum 3D7

General Information

General Information	Comment	Organism
physiological function	comparison of the infectivity of arg- and wild-type Plasmodium berghei by inoculation of mice using sporozoites dissected from mosquito salivary glands shows a significant reduction in infectivity in the arg- strain 40 h postinfection	Plasmodium berghei

kcat/KM [mM/s]

kcat/KM Value [1/mMs^-1]	kcat/KM Value Maximum [1/mMs^-1]	Substrate	Comment	Organism
2.7	-	L-arginine	mutant dN-PFA-H381A, pH 8.0, 37°C	Plasmodium falciparum 3D7
2.9	-	L-arginine	mutant dN-PFA-C6H, pH 8.0, 37°C	Plasmodium falciparum 3D7
3	-	L-arginine	mutant dN-PFA, pH 7.4, 37°C	Plasmodium falciparum 3D7
80	-	L-arginine	mutant dN-PFA, pH 8.0, 37°C	Plasmodium falciparum 3D7
133	-	L-arginine	mutant dN-PFA, pH 8.5, 37°C	Plasmodium falciparum 3D7