Amine specificity in transpeptidation.  Inhibition of fibrin cross-linking

Lóránd, L.; Rule, N. G.; Ong, Hwei Ling; Furlanetto, Richard W.; Jacobsen, Anne Flem; Downey, Jeanne E.; Öner, N.; Bruner-Lorand, Joyce

doi:10.1021/bi00843a043

Cited by 169 publications

(106 citation statements)

References 29 publications

(19 reference statements)

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“…Crosslinks of this type have been found in numerous mammalian tissues. Examples of extracellular proteins that are known to be cross-linked by e-(y-glutamyl)lysine isopeptide bonds are fibrin during the final stages of blood clotting (3)(4)(5) and keratin in hair and wool (6,7). Among intracellular proteins, e-(y-glutamyl)lysine-crosslinked polymers are formed in erythrocyte membranes (8,9), during senile cataract formation in human lens (10), and in the cornified envelope of terminally differentiated keratinocytes in human epidermis (11).…”

mentioning

confidence: 99%

Brain transglutaminase: in vitro crosslinking of human neurofilament proteins into insoluble polymers.

Selkoe¹,

Abraham²,

Ihara³

1982

Proc. Natl. Acad. Sci. U.S.A.

200

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The accumulation in aged human neurons of insoluble, high molecular weight filamentous polymers apparently linked by nondisulfide covalent bonds led us to examine human brain for the presence of transglutaminase (EC 2.3.2.13) and endogenous protein substrates for this crosslinking enzyme. We demonstrate the presence in brain of a transamidating enzyme that can covalently crosslink brain proteins into insoluble polymers in vitro by forming 'y-glutamyl-e-lysine intermolecular bridges.Brain transglutaminase is Ca2" dependent, has an electrophoretic mobility similar to that of erythrocyte transglutaminase, and is active in human postmortem brain from aged normal individuals and patients with Alzheimer disease (senile dementia). Brain neurofilament fractions incubated in the presence of transglutaminase, Ca2+, and the fluorescent amine dansylcadaverine form a fluorescent, nondisulfide-bonded insoluble polymer; this process is associated with a decrease in the amount of soluble neurofilament polypeptides in the preparation. Electron microscopy of the polymeric material reveals an extensive network ofconnecting fiaments, which can be immunostained with various neurofilament antisera. Cystamine, an inhibitor of transglutaminase, prevents the neurofilament crosslinking. Glial filaments and myelin basic protein can also serve as substrates of brain transglutaminase in vitro. Although Alzheimer disease-type paired helical filaments are not formed under the specific in vitro conditions employed, the data suggest one possible mechanism for the covalent crosslinking of filaments into insoluble polymers during human neuronal aging.

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mentioning

confidence: 99%

Brain transglutaminase: in vitro crosslinking of human neurofilament proteins into insoluble polymers.

Selkoe¹,

Abraham²,

Ihara³

1982

Proc. Natl. Acad. Sci. U.S.A.

200

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“…Human TGase was isolated from erythrocytes by affinity chromatography as described (Radek et al, 1993;Murthy et al, l998a). Dansylcadaverine (DC) (Lorand et al, 1968;Murthy et al, 1994) and Gin-containing dansyle-aminocaproyl-Gln-Gln-Ile-Val (darisyl-c-aca-QQIV) peptide (Lorand et al, 1991, l992a) were prepared and kindly provided by Dr. K. N. Parameswaran (Northwestern University Medical School, Chicago, IL, U.S.A.), whereas L-(tosylamido-2-phenyl ) ethylchloromethyl ketone-treated trypsin (Worthington Biochemicals, Freehold, NJ, U.S.A.) and endoproteinase Glu-C (Boehringer Mannheim, Indianapolis, IN, U.S.A.) were obtained from commercial sources.…”

Section: Methodsmentioning

confidence: 99%

Cross‐Linking Sites of the Human Tau Protein, Probed by Reactions with Human Transglutaminase

Murthy

Wilson

Lukas

et al. 1998

Journal of Neurochemistry

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A portion of the neurofibrillary tangles of Alzheimer's disease has the characteristics of cross-linked protein. Because the principal component of these lesions is the microtubule-associated protein tau, and because a major source of cross-linking activity within neurons is supplied by tissue transglutaminase (TGase), it has been postulated that isopeptide bond formation is a major posttranslational modification leading to the formation of insoluble neurofibrillary tangles. Here we have mapped the sites on two isoforms of human tau protein (r23 and 40) capable of participating in human TGase-mediated isopeptide bond formation. Using dansyl-labeled fluorescent probes, it was shown that eight Gin residues can function as amine acceptor residues, with two major sites being Gin 351 and Gin424. In addition, 10 Lys residues were identified as amine donors, most of which are clustered adjacent to the microtubule-binding repeats of tau in regions known to be solvent accessible in filamentous tau. The distribution of amine donors correlated closely with that of Arg residues, suggesting a link between neighboring positive charge and the TGase selectivity for donor sites in the protein substrate. Apart from revealing the sites that can be cross-linked during the TGase-catalyzed assembly of tau filaments, the results suggest a topography for the tau monomers so assembled. Key Words: Alzheimer's disease-Neurofibrillary tangles-Paired helical filament-Tau protein -Transglutaminase.

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“…The covalent cross-linking of fibrin units occurs through an amide exchange reaction (transamidation) between select glutamine and lysine residues of neighboring protein molecules [27][28][29][30][31] (Figure 3a). As a result, a few strategically located N ⑀ (␥-glutamyl)lysine side chain bridges are formed.…”

Section: The Urea-insoluble Clotmentioning

confidence: 99%

Sol Sherry Lecture in Thrombosis

Lóránd

2000

ATVB

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Amine specificity in transpeptidation. Inhibition of fibrin cross-linking

Cited by 169 publications

References 29 publications

Brain transglutaminase: in vitro crosslinking of human neurofilament proteins into insoluble polymers.

Brain transglutaminase: in vitro crosslinking of human neurofilament proteins into insoluble polymers.

Cross‐Linking Sites of the Human Tau Protein, Probed by Reactions with Human Transglutaminase

Sol Sherry Lecture in Thrombosis

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