A transition state analog for phosphate diester cleavage catalyzed by a small enzyme-like metal ion complex

Meng Yin Yang; Janet R. Morrow; John P. Richard

doi:10.1016/j.bioorg.2007.02.003

A transition state analog for phosphate diester cleavage catalyzed by a small enzyme-like metal ion complex

Chemistry

SUNY Buffalo

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

26 Scopus citations

Abstract

The values of K_i for methylphosphate dianion (MP^2-) inhibition of the cleavage of 2-hydroxypropyl-4-nitrophenyl phosphate (HpPNP) catalyzed by 1,3-bis(1,4,7-triazacyclonon-1-yl)-2-hydroxypropane (Zn₂(1)(H₂O)) approach a small limiting value of 6 μM at pH < pK_a = 7.8 for deprotonation of the catalyst to form Zn₂(1)(HO^-). There is a 1600-fold difference in the affinity of a phosphate diester monoanion (diethylphosphate) and phosphate monester dianion (MP^2-) for Zn₂(1)(H₂O). This suggests that the latter is an analog for the transition state dianion for the cleavage reaction of HpPNP and other phosphate diesters. The observation that this transition state analog binds selectively to Zn₂(1)(H₂O) provides strong evidence that this is the active form of the catalyst which binds selectively to the ionized substrate. The efficiency of catalysis of the cleavage of phosphate diesters by Zn₂(1)(H₂O) and proteins is compared.

Original language	English
Pages (from-to)	366-374
Number of pages	9
Journal	Bioorganic Chemistry
Volume	35
Issue number	5
DOIs	https://doi.org/10.1016/j.bioorg.2007.02.003
State	Published - Oct 2007

Keywords

Metal ion catalysis
Phosphate diester
RNA analog

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10.1016/j.bioorg.2007.02.003

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title = "A transition state analog for phosphate diester cleavage catalyzed by a small enzyme-like metal ion complex",

abstract = "The values of Ki for methylphosphate dianion (MP2-) inhibition of the cleavage of 2-hydroxypropyl-4-nitrophenyl phosphate (HpPNP) catalyzed by 1,3-bis(1,4,7-triazacyclonon-1-yl)-2-hydroxypropane (Zn2(1)(H2O)) approach a small limiting value of 6 μM at pH < pKa = 7.8 for deprotonation of the catalyst to form Zn2(1)(HO-). There is a 1600-fold difference in the affinity of a phosphate diester monoanion (diethylphosphate) and phosphate monester dianion (MP2-) for Zn2(1)(H2O). This suggests that the latter is an analog for the transition state dianion for the cleavage reaction of HpPNP and other phosphate diesters. The observation that this transition state analog binds selectively to Zn2(1)(H2O) provides strong evidence that this is the active form of the catalyst which binds selectively to the ionized substrate. The efficiency of catalysis of the cleavage of phosphate diesters by Zn2(1)(H2O) and proteins is compared.",

keywords = "Metal ion catalysis, Phosphate diester, RNA analog",

author = "Yang, \{Meng Yin\} and Morrow, \{Janet R.\} and Richard, \{John P.\}",

year = "2007",

month = oct,

doi = "10.1016/j.bioorg.2007.02.003",

language = "English",

volume = "35",

pages = "366--374",

journal = "Bioorganic Chemistry",

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T1 - A transition state analog for phosphate diester cleavage catalyzed by a small enzyme-like metal ion complex

AU - Yang, Meng Yin

AU - Morrow, Janet R.

AU - Richard, John P.

PY - 2007/10

Y1 - 2007/10

N2 - The values of Ki for methylphosphate dianion (MP2-) inhibition of the cleavage of 2-hydroxypropyl-4-nitrophenyl phosphate (HpPNP) catalyzed by 1,3-bis(1,4,7-triazacyclonon-1-yl)-2-hydroxypropane (Zn2(1)(H2O)) approach a small limiting value of 6 μM at pH < pKa = 7.8 for deprotonation of the catalyst to form Zn2(1)(HO-). There is a 1600-fold difference in the affinity of a phosphate diester monoanion (diethylphosphate) and phosphate monester dianion (MP2-) for Zn2(1)(H2O). This suggests that the latter is an analog for the transition state dianion for the cleavage reaction of HpPNP and other phosphate diesters. The observation that this transition state analog binds selectively to Zn2(1)(H2O) provides strong evidence that this is the active form of the catalyst which binds selectively to the ionized substrate. The efficiency of catalysis of the cleavage of phosphate diesters by Zn2(1)(H2O) and proteins is compared.

AB - The values of Ki for methylphosphate dianion (MP2-) inhibition of the cleavage of 2-hydroxypropyl-4-nitrophenyl phosphate (HpPNP) catalyzed by 1,3-bis(1,4,7-triazacyclonon-1-yl)-2-hydroxypropane (Zn2(1)(H2O)) approach a small limiting value of 6 μM at pH < pKa = 7.8 for deprotonation of the catalyst to form Zn2(1)(HO-). There is a 1600-fold difference in the affinity of a phosphate diester monoanion (diethylphosphate) and phosphate monester dianion (MP2-) for Zn2(1)(H2O). This suggests that the latter is an analog for the transition state dianion for the cleavage reaction of HpPNP and other phosphate diesters. The observation that this transition state analog binds selectively to Zn2(1)(H2O) provides strong evidence that this is the active form of the catalyst which binds selectively to the ionized substrate. The efficiency of catalysis of the cleavage of phosphate diesters by Zn2(1)(H2O) and proteins is compared.

KW - Metal ion catalysis

KW - Phosphate diester

KW - RNA analog

UR - https://www.scopus.com/pages/publications/34548118293

U2 - 10.1016/j.bioorg.2007.02.003

DO - 10.1016/j.bioorg.2007.02.003

M3 - Article

C2 - 17434205

AN - SCOPUS:34548118293

SN - 0045-2068

VL - 35

SP - 366

EP - 374

JO - Bioorganic Chemistry

JF - Bioorganic Chemistry

IS - 5

ER -

A transition state analog for phosphate diester cleavage catalyzed by a small enzyme-like metal ion complex

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Keywords

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