Reductive alkylation of amino groups in proteins

Means, Gary E.; Feeney, Robert E.

doi:10.1021/bi00846a023

Cited by 671 publications

(292 citation statements)

References 29 publications

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“…Swiss female mice (26-28 g) were injected i.v. with 2 pg/g body wt of "'C-1abelled AF (7 X lo5 dpm/mg) prepared according to [36]. Cold AF or conjugates were administered simultaneously with [14C]AF at 20 pg/g body wt except in expt 5 in which the conjugate was injected at 33 pg/g (an amount equimolecular to 20 pg AF).…”

Section: [Methyl-3h/thymidinementioning

confidence: 99%

Hepatocyte targeting of adenine‐9‐β‐D‐arabinofuranoside 5′‐monophosphate (ara‐AMP) coupled to lactosaminated albumin

Fiume¹,

Busi²,

Mattioli³

et al. 1981

FEBS Letters

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Section: [Methyl-3h/thymidinementioning

confidence: 99%

Hepatocyte targeting of adenine‐9‐β‐D‐arabinofuranoside 5′‐monophosphate (ara‐AMP) coupled to lactosaminated albumin

Fiume¹,

Busi²,

Mattioli³

et al. 1981

FEBS Letters

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“…That may be due to the fact that the somatotropic activity is more strictly located. As methylation of the amino groups produced only a very slight change in pK [15], the drastic loss of binding activity of oCS to somatotropic receptors after methylation must be attributed to steric hindrance resulting from the introduction of methyl groups on f-NHz. Thus, some lysine residues appear to be essential for the growth hormone activity of ocs.…”

Section: Acetimidinationmentioning

confidence: 96%

“…The solutions were dialyzed against a pyridine solution (1%) and freeze-dried. Determinations of lysine, methyl-and ethyllysine were made using a Technicon autoanalyzer and elution gradients containing isopropanol [15,16]. A blank for biological assays was prepared by treating hormone with borohydride and borate buffer (pH 9, no added aldehyde).…”

Section: Reductive Alkylationmentioning

confidence: 99%

Involvement of lysine residues in the binding of ovine chorionic somatomammotropin to lactogenic and somatotropic receptors

Chêne¹,

Martal²

1984

FEBS Letters

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The biological activities of several ovine chorionic somatomammotropin (oCS) derivatives obtained by chemical modification of the lysine residues were studied by radioreceptor assays using rabbit mammary homogenates (lactogenic activity, L.A.) and liver homogenates (somatotropic activity, S.A.). Even if the control treatment with BHI markedly decreased the L.A., it was clear that methylation mainly affected the S.A. and that ethylation reduced both activities. Guanidination inactivated almost completely both activities and acetimidination at a very low degree (3 of 14 lysines) led to less than 50% of both activities. These results show the involvement of lysine residues in the interaction of oCS with lactogenic and somatotropic receptors. Ovine chorionic somatomammotropin Prolactin Growth hormone Lysine residue Receptor

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“…Such adducts would be expected considering that imines may form spontaneously at other sites bearing a primary amino group. 46,47 Scheme 2. Proposed Mechanisms for Inactivation of MR by 3-HP Giving Rise to an 86 Da Adduct VERSION; this is the author's final, peer-reviewed manuscript. The published version may be accessed by following the link in the citation at the bottom of the page.…”

mentioning

confidence: 99%

Inactivation of Mandelate Racemase by 3-Hydroxypyruvate Reveals a Potential Mechanistic Link between Enzyme Superfamilies

et al. 2015

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Mandelate racemase (MR), a member of the enolase superfamily, catalyzes the Mg 2+ -dependent interconversion of the enantiomers of mandelate. Several α-keto acids are modest competitive inhibitors of MR [e.g., mesoxalate (Ki = 1.8 ± 0.3 mM) and 3-fluoropyruvate (Ki = 1.3 ± 0.1 mM)], but, surprisingly, 3-hydroxypyruvate (3-HP) is an irreversible, time-dependent inhibitor (kinact/KI = 83 ± 8 M -1 s -1 ). Protection from inactivation by the competitive inhibitor benzohydroxamate, trypsinolysis and electrospray ionization tandem mass spectrometry analyses, and X-ray crystallographic studies reveal that 3-HP undergoes Schiff-base formation with Lys 166 at the active site, followed by formation of an aldehyde/enol(ate) adduct. Such a reaction is unprecedented in the enolase superfamily and may be a relic of an activity possessed by a promiscuous progenitor enzyme. The ability of MR to form and deprotonate a Schiff-base intermediate furnishes a previously unrecognized mechanistic link to other α/β-barrel enzymes utilizing Schiff-base chemistry and is in accord with the sequence-and structure-based hypothesis that members of the metal-dependent enolase superfamily and the Schiff-baseforming N-acetylneuraminate lyase superfamily and aldolases share a common ancestor.One of the first enzyme superfamilies recognized was the enolase superfamily, 1 whose members share a common partial reaction (i.e., the metal-assisted, Brønsted-base-catalyzed abstraction of the α-proton from a carboxylate substrate to form an enolate) 2-5 and a common protein fold [i.e., a modified (α/β)8-barrel (TIM barrel) bearing the catalytic residues at the C-terminal ends of the β-strands and an N-terminal domain that caps the active site conferring substrate specificity and excluding solvent]. [6][7][8] Studies of members of the enolase superfamily have afforded important insights into enzyme evolution and developing strategies for assigning the correct functions to proteins identified in genome projects. 3,[9][10][11][12] The well-characterized NOT THE PUBLISHED VERSION; this is the author's final, peer-reviewed manuscript. The published version may be accessed by following the link in the citation at the bottom of the page.Biochemistry, Vol 54, No. 17 (May 5, 2015): pg. 2747-2757. DOI. This article is © American Chemical Society and permission has been granted for this version to appear in e-Publications@Marquette. American Chemical Society does not grant permission for this article to be further copied/distributed or hosted elsewhere without the express permission from American Chemical Society. 3archetype of this superfamily, mandelate racemase (MR, EC 5.1.2.2) from Pseudomonas putida, catalyzes the Mg 2+ -dependent, 1,1-proton transfer reaction that interconverts the enantiomers of mandelate and has served as a useful paradigm for understanding how enzymes catalyze the rapid α-deprotonation of a carbon acid substrate with a relatively high pKa value. 13 MR utilizes a two-base mechanism with Lys 166 and His 297 abstracting the α-proton fr...

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Reductive alkylation of amino groups in proteins

Cited by 671 publications

References 29 publications

Hepatocyte targeting of adenine‐9‐β‐D‐arabinofuranoside 5′‐monophosphate (ara‐AMP) coupled to lactosaminated albumin

Hepatocyte targeting of adenine‐9‐β‐D‐arabinofuranoside 5′‐monophosphate (ara‐AMP) coupled to lactosaminated albumin

Involvement of lysine residues in the binding of ovine chorionic somatomammotropin to lactogenic and somatotropic receptors

Inactivation of Mandelate Racemase by 3-Hydroxypyruvate Reveals a Potential Mechanistic Link between Enzyme Superfamilies

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