1PQ3

Human Arginase II: Crystal Structure and Physiological Role in Male and Female Sexual Arousal

Summary for 1PQ3

• Entry DOI: 10.2210/pdb1pq3/pdb
• Descriptor: Arginase II, mitochondrial precursor, SULFATE ION, MANGANESE (II) ION, ... (6 entities in total)
• Functional Keywords: biosynthetic protein, hydrolase
• Biological source: Homo sapiens (human)
• Cellular location: Mitochondrion: P78540
• Total number of polymer chains: 6
• Total formula weight: 202927.62

Authors

Cama, E.,Colleluori, D.M.,Emig, F.A.,Shin, H.,Kim, S.W.,Kim, N.N.,Traish, A.M.,Ash, D.E.,Christianson, D.W. (deposition date: 2003-06-17, release date: 2003-08-12, Last modification date: 2024-02-14)

Primary citation

Cama, E.,Colleluori, D.M.,Emig, F.A.,Shin, H.,Kim, S.W.,Kim, N.N.,Traish, A.M.,Ash, D.E.,Christianson, D.W.
Human Arginase II: Crystal Structure and Physiological Role in Male and Female Sexual Arousal
Biochemistry, 42:8445-8451, 2003

PubMed Abstract: Arginase is a binuclear manganese metalloenzyme that catalyzes the hydrolysis of l-arginine to form l-ornithine and urea. The X-ray crystal structure of a fully active, truncated form of human arginase II complexed with a boronic acid transition state analogue inhibitor has been determined at 2.7 A resolution. This structure is consistent with the hydrolysis of l-arginine through a metal-activated hydroxide mechanism. Given that human arginase II appears to play a role in regulating l-arginine bioavailability to NO synthase in human penile corpus cavernosum smooth muscle, the inhibition of human arginase II is a potential new strategy for the treatment of erectile dysfunction [Kim, N. N., Cox, J. D., Baggio, R. F., Emig, F. A., Mistry, S., Harper, S. L., Speicher, D. W., Morris, S. M., Ash, D. E., Traish, A. M., and Christianson, D. W. (2001) Biochemistry 40, 2678-2688]. Since NO synthase is found in human clitoral corpus cavernosum and vagina, we hypothesized that human arginase II is similarly present in these tissues and functions to regulate l-arginine bioavailability to NO synthase. Accordingly, hemodynamic studies conducted with a boronic acid arginase inhibitor in vivo are summarized, suggesting that the extrahepatic arginase plays a role in both male and female sexual arousal. Therefore, arginase II is a potential target for the treatment of male and female sexual arousal disorders.

PubMed: 12859189
DOI: 10.1021/bi034340j

Experimental method

X-RAY DIFFRACTION (2.7 Å)