DOI: 10.1002/jcc.540110703. Mechanistic aspects of biological redox reactions involving NADH 2: A combined semiempirical and <i>ab initio</i> study of hydride‐ion transfer between the NADH analogue, 1‐methyl‐dihydronicotinamide, and folate and dihydrofolate analogue substrates of dihydrofolate reductase

Mechanistic aspects of biological redox reactions involving NADH 2: A combined semiempirical and ab initio study of hydride‐ion transfer between the NADH analogue, 1‐methyl‐dihydronicotinamide, and folate and dihydrofolate analogue substrates of dihydrofolate reductase

10.1002/jcc.540110703

Crossref journal-article

Wiley

Journal of Computational Chemistry (311)

Abstract

AbstractAs part of a study of factors controlling biological redox reactions of nicotinamide cofactors [nicotinamide adenine dinucleotide (phosphate) NAD(P)H], we have investigated the effect on a model reaction of the conformational state (cis or trans) of the carboxamide side chain, using quantum chemical methods. The reaction is that for the enzyme dihydrofolate reductase between the NADPH analogue, 1‐methyl‐dihydronicotinamide, and the protonated forms of the folate and dihydrofolate substrate analogues, pyrazine and dihydropyrazine. Some calculations on pterin and dihydropterin substrate analogues were also carried out in order to gauge the effects of inter‐ring coupling. The influence of carboxamide side‐chain conformation of nicotinamide on the energetics of the hydride‐ion transfer, and on the structures of the transition states and stable intermolecular‐interaction complexes, are examined as a function of the orientation of approach of the reactants. These approach geometries include those corresponding to the observed binding of cofactor and either substrate or inhibitor in the enzyme active site. Reactant, product, reactants‐complex, and transition‐state geometries were optimized at the semiempirical AM1 level, while ab initio SCF/STO‐3G and SCF/3‐21G single‐point calculations were carried out at the AM1 optimized geometries for all species, as well as full geometry optimizations for isolated reactants and products. The results show that reactants‐complex and transition‐state energies are lower for the trans conformer of dihydronicotinamide than for the cis conformer, due to more favorable H‐bonding or electrostatic interactions with the protonated substrate. Also, consideration of the structural parameters, including reaction coordinate bond lengths, ring geometries, and charge distributions, indicate that the trans transition states are more product‐like than those for the cis. For the (trans) approaches corresponding to the enzymic orientation for substrate, the intermolecular interaction for the folate reaction lacks the stabilizing influence of the formal H‐bond which is present for the dihydrofolate reaction, and consequently the reactants‐complex and transition state are less stable.

Bibliography

Cummins, P. L., & Gready, J. E. (1990). Mechanistic aspects of biological redox reactions involving NADH 2: A combined semiempirical and ab initio study of hydrideâion transfer between the NADH analogue, 1âmethylâdihydronicotinamide, and folate and dihydrofolate analogue substrates of dihydrofolate reductase. Journal of Computational Chemistry, 11(7), 791â804. Portico.

Authors 2

Peter L. Cummins (first)
Jill E. Gready (additional)

References 49 Referenced 26

10.1021/ja00412a002
10.1021/ja00412a003 / J. Am. Chem. Soc. by Donkersloot M. C. A. (1981)
10.1021/ja00343a034
10.1016/0166-1280(88)80068-X
10.1021/ja00220a058
10.1021/ja00237a050
10.1016/0022-2836(76)90311-9
10.1021/ja00324a035
10.1002/jcc.540070604
10.1016/0166-1280(89)80032-6
{'key': 'e_1_2_1_11_2', 'first-page': '355', 'volume-title': 'Pteridine Chemistry', 'author': 'Huennekens F. M.', 'year': '1964'} / Pteridine Chemistry by Huennekens F. M. (1964)
10.1021/bi00339a008
10.1016/S0021-9258(18)33498-7
10.1021/bi00320a014
10.1021/bi00336a030
10.1016/S0021-9258(19)40703-5
10.1107/S0567740874002950
10.1107/S0365110X61001583
10.1021/ja00394a031
10.1021/ja00834a001
10.1002/jcc.540080808
D. A.Matthews S. J.Oatley andJ.Kraut unpublished results.
C.Bystroff S. J.Oatley andJ.Kraut Biochem. in press.
10.1016/S0021-9258(18)33497-5
10.1021/ja00299a024
10.1021/ja00457a004
10.1021/ja00839a001
10.1063/1.1672392
10.1021/ja00523a008
P. L.Cummins SYDPAC unpublished work.
10.1002/jcc.540100712
10.1016/S0022-2860(84)87198-7
R. F.HoutJr. M. M.Francl S. D.Kahn K. D.Dobbs E. S.Blurock W. J.Pietro M. P.McGrath R.Steckler W. J.Hehre GAUSSIAN‐85 Univ. of Illinois (Urbana‐Champaign) and Univ. of California (Irvine) 1988.
10.1002/jcc.540100111 / J. Comp. Chem. by Haeser M. (1989)
M.Frisch GAUSSIAN‐82Users Manual (Release A Version Sept. 1983) Dept. of Chemistry Carnegie‐Mellon University.
10.1016/0166-1280(84)80007-X
10.1002/jcc.540060507
10.1016/0166-1280(85)87016-0
{'key': 'e_1_2_1_39_2', 'first-page': '85', 'volume-title': 'Chemistry and Biology of Pteridines 1986', 'author': 'Gready J. E.', 'year': '1986'} / Chemistry and Biology of Pteridines 1986 by Gready J. E. (1986)
10.1002/hlca.19820650342
10.1021/ja00267a063
10.1351/pac198961040643
10.1016/0166-1280(88)80155-6
10.1111/j.1432-1033.1988.tb14108.x
10.1039/c39790000922
10.1021/ja00514a041
10.1002/jcc.540050502
10.1002/qua.560310308
Geometries available from authors on request.

Dates

Type	When
Created	20 years, 7 months ago (Jan. 1, 2005, 7:33 p.m.)
Deposited	1 year, 10 months ago (Oct. 22, 2023, 10:44 a.m.)
Indexed	1 year, 7 months ago (Jan. 13, 2024, 1:45 a.m.)
Issued	35 years ago (Aug. 1, 1990)
Published	35 years ago (Aug. 1, 1990)
Published Online	20 years, 11 months ago (Sept. 7, 2004)
Published Print	35 years ago (Aug. 1, 1990)

Funders 0

None

BibTeX

@article{Cummins_1990, title={Mechanistic aspects of biological redox reactions involving NADH 2: A combined semiempirical and ab initio study of hydride‐ion transfer between the NADH analogue, 1‐methyl‐dihydronicotinamide, and folate and dihydrofolate analogue substrates of dihydrofolate reductase}, volume={11}, ISSN={1096-987X}, url={http://dx.doi.org/10.1002/jcc.540110703}, DOI={10.1002/jcc.540110703}, number={7}, journal={Journal of Computational Chemistry}, publisher={Wiley}, author={Cummins, Peter L. and Gready, Jill E.}, year={1990}, month=aug, pages={791–804} }

JSON

{
  "indexed": {
    "date-parts": [
      [
        2024,
        1,
        13
      ]
    ],
    "date-time": "2024-01-13T06:45:08Z",
    "timestamp": 1705128308882
  },
  "reference-count": 49,
  "publisher": "Wiley",
  "issue": "7",
  "license": [
    {
      "start": {
        "date-parts": [
          [
            2004,
            9,
            7
          ]
        ],
        "date-time": "2004-09-07T00:00:00Z",
        "timestamp": 1094515200000
      },
      "content-version": "vor",
      "delay-in-days": 5151,
      "URL": "http://onlinelibrary.wiley.com/termsAndConditions#vor"
    }
  ],
  "content-domain": {
    "domain": [],
    "crossmark-restriction": false
  },
  "published-print": {
    "date-parts": [
      [
        1990,
        8
      ]
    ]
  },
  "abstract": "<jats:title>Abstract</jats:title><jats:p>As part of a study of factors controlling biological redox reactions of nicotinamide cofactors [nicotinamide adenine dinucleotide (phosphate) NAD(P)H], we have investigated the effect on a model reaction of the conformational state (<jats:italic>cis</jats:italic> or <jats:italic>trans</jats:italic>) of the carboxamide side chain, using quantum chemical methods. The reaction is that for the enzyme dihydrofolate reductase between the NADPH analogue, 1\u2010methyl\u2010dihydronicotinamide, and the protonated forms of the folate and dihydrofolate substrate analogues, pyrazine and dihydropyrazine. Some calculations on pterin and dihydropterin substrate analogues were also carried out in order to gauge the effects of inter\u2010ring coupling. The influence of carboxamide side\u2010chain conformation of nicotinamide on the energetics of the hydride\u2010ion transfer, and on the structures of the transition states and stable intermolecular\u2010interaction complexes, are examined as a function of the orientation of approach of the reactants. These approach geometries include those corresponding to the observed binding of cofactor and either substrate or inhibitor in the enzyme active site. Reactant, product, reactants\u2010complex, and transition\u2010state geometries were optimized at the semiempirical AM1 level, while <jats:italic>ab initio</jats:italic> SCF/STO\u20103G and SCF/3\u201021G single\u2010point calculations were carried out at the AM1 optimized geometries for all species, as well as full geometry optimizations for isolated reactants and products. The results show that reactants\u2010complex and transition\u2010state energies are lower for the <jats:italic>trans</jats:italic> conformer of dihydronicotinamide than for the <jats:italic>cis</jats:italic> conformer, due to more favorable H\u2010bonding or electrostatic interactions with the protonated substrate. Also, consideration of the structural parameters, including reaction coordinate bond lengths, ring geometries, and charge distributions, indicate that the <jats:italic>trans</jats:italic> transition states are more product\u2010like than those for the <jats:italic>cis.</jats:italic> For the (<jats:italic>trans</jats:italic>) approaches corresponding to the enzymic orientation for substrate, the intermolecular interaction for the folate reaction lacks the stabilizing influence of the formal H\u2010bond which is present for the dihydrofolate reaction, and consequently the reactants\u2010complex and transition state are less stable.</jats:p>",
  "DOI": "10.1002/jcc.540110703",
  "type": "journal-article",
  "created": {
    "date-parts": [
      [
        2005,
        1,
        2
      ]
    ],
    "date-time": "2005-01-02T00:33:07Z",
    "timestamp": 1104625987000
  },
  "page": "791-804",
  "source": "Crossref",
  "is-referenced-by-count": 26,
  "title": "Mechanistic aspects of biological redox reactions involving NADH 2: A combined semiempirical and <i>ab initio</i> study of hydride\u2010ion transfer between the NADH analogue, 1\u2010methyl\u2010dihydronicotinamide, and folate and dihydrofolate analogue substrates of dihydrofolate reductase",
  "prefix": "10.1002",
  "volume": "11",
  "author": [
    {
      "given": "Peter L.",
      "family": "Cummins",
      "sequence": "first",
      "affiliation": []
    },
    {
      "given": "Jill E.",
      "family": "Gready",
      "sequence": "additional",
      "affiliation": []
    }
  ],
  "member": "311",
  "published-online": {
    "date-parts": [
      [
        2004,
        9,
        7
      ]
    ]
  },
  "reference": [
    {
      "key": "e_1_2_1_2_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1021/ja00412a002"
    },
    {
      "key": "e_1_2_1_2_3",
      "doi-asserted-by": "crossref",
      "first-page": "6554",
      "DOI": "10.1021/ja00412a003",
      "author": "Donkersloot M. C. A.",
      "year": "1981",
      "journal-title": "J. Am. Chem. Soc."
    },
    {
      "key": "e_1_2_1_3_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1021/ja00343a034"
    },
    {
      "key": "e_1_2_1_4_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1016/0166-1280(88)80068-X"
    },
    {
      "key": "e_1_2_1_5_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1021/ja00220a058"
    },
    {
      "key": "e_1_2_1_6_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1021/ja00237a050"
    },
    {
      "key": "e_1_2_1_7_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1016/0022-2836(76)90311-9"
    },
    {
      "key": "e_1_2_1_8_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1021/ja00324a035"
    },
    {
      "key": "e_1_2_1_9_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1002/jcc.540070604"
    },
    {
      "key": "e_1_2_1_10_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1016/0166-1280(89)80032-6"
    },
    {
      "key": "e_1_2_1_11_2",
      "first-page": "355",
      "volume-title": "Pteridine Chemistry",
      "author": "Huennekens F. M.",
      "year": "1964"
    },
    {
      "key": "e_1_2_1_12_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1021/bi00339a008"
    },
    {
      "key": "e_1_2_1_13_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1016/S0021-9258(18)33498-7"
    },
    {
      "key": "e_1_2_1_14_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1021/bi00320a014"
    },
    {
      "key": "e_1_2_1_15_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1021/bi00336a030"
    },
    {
      "key": "e_1_2_1_16_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1016/S0021-9258(19)40703-5"
    },
    {
      "key": "e_1_2_1_17_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1107/S0567740874002950"
    },
    {
      "key": "e_1_2_1_18_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1107/S0365110X61001583"
    },
    {
      "key": "e_1_2_1_19_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1021/ja00394a031"
    },
    {
      "key": "e_1_2_1_20_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1021/ja00834a001"
    },
    {
      "key": "e_1_2_1_21_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1002/jcc.540080808"
    },
    {
      "key": "e_1_2_1_22_2",
      "unstructured": "D. A.Matthews S. J.Oatley andJ.Kraut unpublished results."
    },
    {
      "key": "e_1_2_1_23_2",
      "unstructured": "C.Bystroff S. J.Oatley andJ.Kraut Biochem. in press."
    },
    {
      "key": "e_1_2_1_24_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1016/S0021-9258(18)33497-5"
    },
    {
      "key": "e_1_2_1_25_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1021/ja00299a024"
    },
    {
      "key": "e_1_2_1_26_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1021/ja00457a004"
    },
    {
      "key": "e_1_2_1_27_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1021/ja00839a001"
    },
    {
      "key": "e_1_2_1_28_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1063/1.1672392"
    },
    {
      "key": "e_1_2_1_29_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1021/ja00523a008"
    },
    {
      "key": "e_1_2_1_30_2",
      "unstructured": "P. L.Cummins SYDPAC unpublished work."
    },
    {
      "key": "e_1_2_1_31_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1002/jcc.540100712"
    },
    {
      "key": "e_1_2_1_32_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1016/S0022-2860(84)87198-7"
    },
    {
      "key": "e_1_2_1_33_2",
      "unstructured": "R. F.HoutJr. M. M.Francl S. D.Kahn K. D.Dobbs E. S.Blurock W. J.Pietro M. P.McGrath R.Steckler W. J.Hehre GAUSSIAN\u201085 Univ. of Illinois (Urbana\u2010Champaign) and Univ. of California (Irvine) 1988."
    },
    {
      "key": "e_1_2_1_34_2",
      "doi-asserted-by": "crossref",
      "first-page": "104",
      "DOI": "10.1002/jcc.540100111",
      "volume": "10",
      "author": "Haeser M.",
      "year": "1989",
      "journal-title": "J. Comp. Chem."
    },
    {
      "key": "e_1_2_1_35_2",
      "unstructured": "M.Frisch GAUSSIAN\u201082Users Manual (Release A Version Sept. 1983) Dept. of Chemistry Carnegie\u2010Mellon University."
    },
    {
      "key": "e_1_2_1_36_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1016/0166-1280(84)80007-X"
    },
    {
      "key": "e_1_2_1_37_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1002/jcc.540060507"
    },
    {
      "key": "e_1_2_1_38_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1016/0166-1280(85)87016-0"
    },
    {
      "key": "e_1_2_1_39_2",
      "first-page": "85",
      "volume-title": "Chemistry and Biology of Pteridines 1986",
      "author": "Gready J. E.",
      "year": "1986"
    },
    {
      "key": "e_1_2_1_40_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1002/hlca.19820650342"
    },
    {
      "key": "e_1_2_1_41_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1021/ja00267a063"
    },
    {
      "key": "e_1_2_1_42_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1351/pac198961040643"
    },
    {
      "key": "e_1_2_1_43_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1016/0166-1280(88)80155-6"
    },
    {
      "key": "e_1_2_1_44_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1111/j.1432-1033.1988.tb14108.x"
    },
    {
      "key": "e_1_2_1_45_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1039/c39790000922"
    },
    {
      "key": "e_1_2_1_46_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1021/ja00514a041"
    },
    {
      "key": "e_1_2_1_47_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1002/jcc.540050502"
    },
    {
      "key": "e_1_2_1_48_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1002/qua.560310308"
    },
    {
      "key": "e_1_2_1_49_2",
      "unstructured": "Geometries available from authors on request."
    }
  ],
  "container-title": "Journal of Computational Chemistry",
  "original-title": [],
  "language": "en",
  "link": [
    {
      "URL": "https://api.wiley.com/onlinelibrary/tdm/v1/articles/10.1002%2Fjcc.540110703",
      "content-type": "unspecified",
      "content-version": "vor",
      "intended-application": "text-mining"
    },
    {
      "URL": "https://onlinelibrary.wiley.com/doi/pdf/10.1002/jcc.540110703",
      "content-type": "unspecified",
      "content-version": "vor",
      "intended-application": "similarity-checking"
    }
  ],
  "deposited": {
    "date-parts": [
      [
        2023,
        10,
        22
      ]
    ],
    "date-time": "2023-10-22T14:44:03Z",
    "timestamp": 1697985843000
  },
  "score": 1,
  "resource": {
    "primary": {
      "URL": "https://onlinelibrary.wiley.com/doi/10.1002/jcc.540110703"
    }
  },
  "subtitle": [],
  "short-title": [],
  "issued": {
    "date-parts": [
      [
        1990,
        8
      ]
    ]
  },
  "references-count": 49,
  "journal-issue": {
    "issue": "7",
    "published-print": {
      "date-parts": [
        [
          1990,
          8
        ]
      ]
    }
  },
  "alternative-id": [
    "10.1002/jcc.540110703"
  ],
  "URL": "http://dx.doi.org/10.1002/jcc.540110703",
  "relation": {},
  "ISSN": [
    "0192-8651",
    "1096-987X"
  ],
  "subject": [],
  "container-title-short": "J Comput Chem",
  "published": {
    "date-parts": [
      [
        1990,
        8
      ]
    ]
  }
}