Direct experimental evidence for competitive inhibition of dihydrofolate reductase by methotrexate

Mark C. Waltham; John W. Holland; Scott C. Robinson; Donald J. Winzor; Peter F. Nixon

doi:10.1016/0006-2952(88)90225-0

Direct experimental evidence for competitive inhibition of dihydrofolate reductase by methotrexate

Mark C. Waltham, John W. Holland, Scott C. Robinson, Donald J. Winzor, Peter F. Nixon

Research output: Contribution to journal › Article › Research › peer-review

11 Citations (Scopus)

Abstract

Steady-state enzyme kinetic techniques at very low enzyme concentration (0.4 nM) were used successfully to measure the inhibition constant (53 pM) for the dissociation of methotrexate from the ternary complex of methotrexate, NADPH and dihydrofolate reductase from Lactobacillus casei; and to demonstrate unequivocally that the inhibition was, indeed, competitive with respect to dihydrofolate.

Original language	English
Pages (from-to)	535-539
Number of pages	5
Journal	Biochemical Pharmacology
Volume	37
Issue number	3
DOIs	https://doi.org/10.1016/0006-2952(88)90225-0
Publication status	Published - 1 Feb 1988
Externally published	Yes

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10.1016/0006-2952(88)90225-0

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title = "Direct experimental evidence for competitive inhibition of dihydrofolate reductase by methotrexate",

abstract = "Steady-state enzyme kinetic techniques at very low enzyme concentration (0.4 nM) were used successfully to measure the inhibition constant (53 pM) for the dissociation of methotrexate from the ternary complex of methotrexate, NADPH and dihydrofolate reductase from Lactobacillus casei; and to demonstrate unequivocally that the inhibition was, indeed, competitive with respect to dihydrofolate.",

author = "Waltham, \{Mark C.\} and Holland, \{John W.\} and Robinson, \{Scott C.\} and Winzor, \{Donald J.\} and Nixon, \{Peter F.\}",

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T1 - Direct experimental evidence for competitive inhibition of dihydrofolate reductase by methotrexate

AU - Waltham, Mark C.

AU - Holland, John W.

AU - Robinson, Scott C.

AU - Winzor, Donald J.

AU - Nixon, Peter F.

PY - 1988/2/1

Y1 - 1988/2/1

N2 - Steady-state enzyme kinetic techniques at very low enzyme concentration (0.4 nM) were used successfully to measure the inhibition constant (53 pM) for the dissociation of methotrexate from the ternary complex of methotrexate, NADPH and dihydrofolate reductase from Lactobacillus casei; and to demonstrate unequivocally that the inhibition was, indeed, competitive with respect to dihydrofolate.

AB - Steady-state enzyme kinetic techniques at very low enzyme concentration (0.4 nM) were used successfully to measure the inhibition constant (53 pM) for the dissociation of methotrexate from the ternary complex of methotrexate, NADPH and dihydrofolate reductase from Lactobacillus casei; and to demonstrate unequivocally that the inhibition was, indeed, competitive with respect to dihydrofolate.

UR - https://www.scopus.com/pages/publications/0023853567

U2 - 10.1016/0006-2952(88)90225-0

DO - 10.1016/0006-2952(88)90225-0

M3 - Article

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AN - SCOPUS:0023853567

SN - 0006-2952

VL - 37

SP - 535

EP - 539

JO - Biochemical Pharmacology

JF - Biochemical Pharmacology

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ER -

Direct experimental evidence for competitive inhibition of dihydrofolate reductase by methotrexate

Abstract

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