Full quantum-mechanical structure of the human protein Metallothionein-2

Research output: Contribution to journalJournal articleResearchpeer-review

Abstract

Metallothioneins (MT) are small, metal-binding proteins with diverse functions related to metal ion homeostasis. This paper presents the full 384–388-atom structures of the two native Zn(II)- and the Cd(II)-containing domains of human MT2, optimized with density functional theory. The presented structures are accurate to ~0.03Å for bond lengths and thus provide new physical insight into the detailed electronic structures of MTs, in particular with accurate accounts of bridging vs. terminal bonds not available from NMR or EXAFS. The MT protein enhances the asymmetry, as compared to the protein-free clusters, causing a hierarchy in binding that most likely allows MTs to transfer ions to multiple targets in vivo. The protein polarization is substantial and occurs primarily via the terminal sulfurs, a key mechanism in providing domain-specific electronic structures. The β-domain polarizes its smaller cluster less on average, due to its less polarizable, higher negative charge density, as reflected in longer M&sbnd;S bond lengths and smaller bond orders. This may explain why MT2β is more reactive and dynamic and why MTs have evolved two different-size, asymmetric domains with different metal binding affinities fit for different molecular targets of metal ion transfer.
Original languageEnglish
JournalJournal of Inorganic Biochemistry
Volume107
Issue number1
Pages (from-to)15-24
ISSN0162-0134
DOIs
Publication statusPublished - 2012

Keywords

  • Protein structure
  • Coordination chemistry
  • DFT
  • Metallothionein
  • Zn
  • Cd

Cite this

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title = "Full quantum-mechanical structure of the human protein Metallothionein-2",
abstract = "Metallothioneins (MT) are small, metal-binding proteins with diverse functions related to metal ion homeostasis. This paper presents the full 384–388-atom structures of the two native Zn(II)- and the Cd(II)-containing domains of human MT2, optimized with density functional theory. The presented structures are accurate to ~0.03Å for bond lengths and thus provide new physical insight into the detailed electronic structures of MTs, in particular with accurate accounts of bridging vs. terminal bonds not available from NMR or EXAFS. The MT protein enhances the asymmetry, as compared to the protein-free clusters, causing a hierarchy in binding that most likely allows MTs to transfer ions to multiple targets in vivo. The protein polarization is substantial and occurs primarily via the terminal sulfurs, a key mechanism in providing domain-specific electronic structures. The β-domain polarizes its smaller cluster less on average, due to its less polarizable, higher negative charge density, as reflected in longer M&sbnd;S bond lengths and smaller bond orders. This may explain why MT2β is more reactive and dynamic and why MTs have evolved two different-size, asymmetric domains with different metal binding affinities fit for different molecular targets of metal ion transfer.",
keywords = "Protein structure, Coordination chemistry, DFT, Metallothionein, Zn, Cd",
author = "Kepp, {Kasper Planeta}",
year = "2012",
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language = "English",
volume = "107",
pages = "15--24",
journal = "Journal of Inorganic Biochemistry",
issn = "0162-0134",
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Full quantum-mechanical structure of the human protein Metallothionein-2. / Kepp, Kasper Planeta.

In: Journal of Inorganic Biochemistry, Vol. 107, No. 1, 2012, p. 15-24.

Research output: Contribution to journalJournal articleResearchpeer-review

TY - JOUR

T1 - Full quantum-mechanical structure of the human protein Metallothionein-2

AU - Kepp, Kasper Planeta

PY - 2012

Y1 - 2012

N2 - Metallothioneins (MT) are small, metal-binding proteins with diverse functions related to metal ion homeostasis. This paper presents the full 384–388-atom structures of the two native Zn(II)- and the Cd(II)-containing domains of human MT2, optimized with density functional theory. The presented structures are accurate to ~0.03Å for bond lengths and thus provide new physical insight into the detailed electronic structures of MTs, in particular with accurate accounts of bridging vs. terminal bonds not available from NMR or EXAFS. The MT protein enhances the asymmetry, as compared to the protein-free clusters, causing a hierarchy in binding that most likely allows MTs to transfer ions to multiple targets in vivo. The protein polarization is substantial and occurs primarily via the terminal sulfurs, a key mechanism in providing domain-specific electronic structures. The β-domain polarizes its smaller cluster less on average, due to its less polarizable, higher negative charge density, as reflected in longer M&sbnd;S bond lengths and smaller bond orders. This may explain why MT2β is more reactive and dynamic and why MTs have evolved two different-size, asymmetric domains with different metal binding affinities fit for different molecular targets of metal ion transfer.

AB - Metallothioneins (MT) are small, metal-binding proteins with diverse functions related to metal ion homeostasis. This paper presents the full 384–388-atom structures of the two native Zn(II)- and the Cd(II)-containing domains of human MT2, optimized with density functional theory. The presented structures are accurate to ~0.03Å for bond lengths and thus provide new physical insight into the detailed electronic structures of MTs, in particular with accurate accounts of bridging vs. terminal bonds not available from NMR or EXAFS. The MT protein enhances the asymmetry, as compared to the protein-free clusters, causing a hierarchy in binding that most likely allows MTs to transfer ions to multiple targets in vivo. The protein polarization is substantial and occurs primarily via the terminal sulfurs, a key mechanism in providing domain-specific electronic structures. The β-domain polarizes its smaller cluster less on average, due to its less polarizable, higher negative charge density, as reflected in longer M&sbnd;S bond lengths and smaller bond orders. This may explain why MT2β is more reactive and dynamic and why MTs have evolved two different-size, asymmetric domains with different metal binding affinities fit for different molecular targets of metal ion transfer.

KW - Protein structure

KW - Coordination chemistry

KW - DFT

KW - Metallothionein

KW - Zn

KW - Cd

U2 - 10.1016/j.jinorgbio.2011.11.002

DO - 10.1016/j.jinorgbio.2011.11.002

M3 - Journal article

VL - 107

SP - 15

EP - 24

JO - Journal of Inorganic Biochemistry

JF - Journal of Inorganic Biochemistry

SN - 0162-0134

IS - 1

ER -