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John M. Lowenstein, Ph.D.
Professor of Biochemistry
Regulation and function of HINT
Regulation and Function of Adenosine Production in Heart

Ph.D., London University

contact information
(781) 736-2360

We are studying the function of HINT (histidine triad nucleotide binding) protein, a small regulatory protein which occurs in all forms of life. The mammalian protein has been cloned, expressed, and its crystal structure has been obtained. Function is being determined using knock-outs.

When the work load of the heart is increased or when it becomes hypoxic, it responds by increasing the coronary blood flow. It does this by releasing the vasodilator adenosine which is formed by activation of AMP hydrolysis. The AMPase responsible for producing adenosine in heart is 5'-nucleotidase N-I. The regulatory properties of the enzyme are under investigation.

Selected Publications:

Matsushita K, Morrell CN, Cambien B, Yang SX, Yamakuchi M, Bao C, Hara MR, Quick RA, Cao W, O'Rourke B, Lowenstein JM, Pevsner J, Wagner DD, Lowenstein CJ. (2003) Nitric oxide regulates exocytosis by S-nitrosylation of N-ethylmaleimide-sensitive factor. Cell. 2003 Oct 17;115:139-50. [abstract]

Saura M, Zagora C, McMillan A, Quick RA, Hohenadl CA, Lowenstein JM, Lowenstein CJ. (1999) An Antiviral Mechanism of Nitric Oxide: Inhibition of a Viral Protease. Immunity 10:21-28. [abstract]

Pawelczyk T, Lowenstein JM. (1997) Effect of different species of sphingomyelin on phospholipase C 1 activity. Biochimie 79: 741-748. [abstract]

Ghosh S, Pawelczyk T, Lowenstein JM. (1997) Phospholipase C isoforms delta 1 and delta 3 from human fibroblasts. High-yield expression in Escherichia coli, simple purification, and properties. Protein Expr Purif 9:262-78. [abstract]

Brenner C, Garrison P, Gilmour J, Peisach D, Ringe D, Petsko GA, Lowenstein JM. (1997) Crystal structures of HINT demonstrate that histidine triad proteins are GalT-related nucleotide-binding proteins. Nat Struct Biol 4 :231-8 . [abstract]

Gilmour J, Liang N, Lowenstein JM. (1997) Isolation, cloning and characterization of a low-molecular-mass purine nucleoside- and nucleotide-binding protein. Biochem J 326 ( Pt 2) :471-7 . [abstract]

Richard EA, Ghosh S, Lowenstein JM, Lisman JE. (1997) Ca2+/calmodulin-binding peptides block phototransduction in Limulus ventral photoreceptors: evidence for direct inhibition of phospholipase C. Proc Natl Acad Sci U S A 94:14095-9. [abstract]

 

 

View Complete Publication List on PubMed: John Lowenstein


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