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Chapter02.lyx
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Chapter02.lyx
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#LyX 2.3 created this file. For more info see http://www.lyx.org/
\lyxformat 544
\begin_document
\begin_header
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\begin_body
\begin_layout Chapter
Zinc proteome
\begin_inset CommandInset label
LatexCommand label
name "chap:Zinc proteome"
\end_inset
\end_layout
\begin_layout Section
Properties of zinc
\begin_inset CommandInset label
LatexCommand label
name "sec:properties_of_zinc"
\end_inset
\end_layout
\begin_layout Standard
As have been mentioned in the first sentence of
\begin_inset Flex CT - auto cross-reference
status open
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\begin_inset CommandInset ref
LatexCommand labelonly
reference "subsec:Transition-metal-ions"
plural "false"
caps "false"
noprefix "false"
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transition metals have partially filled
\emph on
d
\emph default
orbital, following this definition one cannot classify zinc as a transition
metal (
\begin_inset Flex CT - auto cross-reference
status open
\begin_layout Plain Layout
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LatexCommand labelonly
reference "fig:Bohr-model-diagram-zinc"
plural "false"
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).
The other definitions of transition metals (i.e.
as chemical elements in the
\emph on
d
\emph default
-block of the periodic table), may include zinc as a transition metal.
The goal of this subsection is not to discuss whether zinc is a transition
metal—
\begin_inset Quotes eld
\end_inset
transition metals
\begin_inset Quotes erd
\end_inset
is a human concept, people are in the habit of categorizing and dividing,
however, it does not matter for the chemical and physical properties of
zinc whether one classifies zinc as a transition metal or not.
The unique properties of zinc and the reason why chemists discuss where
to categorize zinc is due to zinc's electron configuration (
\begin_inset Flex CT - auto cross-reference
status open
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LatexCommand labelonly
reference "fig:Bohr-model-diagram-zinc"
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) – the fully filled
\emph on
d
\emph default
orbitals of zinc are energetically stable, and usually, zinc can lose
\emph on
only
\emph default
4
\emph on
s
\emph default
electrons, leading to the formation of stable Zn(II), which is entirely
different to the biologically active transition metals.
This property of zinc of occurrence in only one oxidation state (2+) prevents
zinc from partaking directly in redox reactions\SpecialChar endofsentence
The total filling of zinc's
\emph on
d
\emph default
orbitals makes zinc a 'spectroscopically quiet' metal – zinc complexes have
no color.
Contrary to metals that have partially filled
\emph on
d-
\emph default
shells, zinc has almost no spectroscopic signature
\begin_inset CommandInset citation
LatexCommand citep
key "Penner-Hahn2005"
literal "true"
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.
This limitation of Zn(II) being redox-inert in biology might produce a
false view of its use by evolution in proteins.
\end_layout
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status open
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distribution-method=quantum,
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insert-missing}
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\begin_layout Plain Layout
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centering
\end_layout
\begin_layout Plain Layout
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bohr{}{Zn}
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\backslash
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elconf{Zn}
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\begin_layout Plain Layout
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LatexCommand label
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Bohr model diagram for of zinc.
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\begin_layout Standard
Zinc, after iron, is the second most abundant
\emph on
d
\emph default
-block element found in proteins,
\begin_inset CommandInset citation
LatexCommand citep
key "Andreini2006,Andreini2006a,Andreini2009"
literal "true"
\end_inset
moreover it is the only
\emph on
d
\emph default
-block element that is found in all classes of enzymes,
\begin_inset CommandInset citation
LatexCommand citep
key "Vallee1990"
literal "true"
\end_inset
this is possible due to being a Lewis acid by Zn(II).
\end_layout
\begin_layout Standard
In solution Zn(II) ions exist in equilibrium as an octahedral hexaaquo complexes
([Zn(H
\begin_inset script subscript
\begin_layout Plain Layout
2
\end_layout
\end_inset
O)
\begin_inset script subscript
\begin_layout Plain Layout
6
\end_layout
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]
\begin_inset script superscript
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2+
\end_layout
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) and as a tetrahedral [Zn(H
\begin_inset script subscript
\begin_layout Plain Layout
2
\end_layout
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O)
\begin_inset script subscript
\begin_layout Plain Layout
4
\end_layout
\end_inset
]
\begin_inset script superscript
\begin_layout Plain Layout
2+
\end_layout
\end_inset
, with equilibrium shifted towards the first one.
\begin_inset CommandInset citation
LatexCommand citep
key "Krezel2016"
literal "true"
\end_inset
Due to the total filling of the
\emph on
d
\emph default
orbitals, the transition between the octahedral to tetrahedral coordination
(typical for complexation by proteins) in the case of zinc does not entail
an energetic penalty,
\begin_inset CommandInset citation
LatexCommand citep
key "Lachenmann2004"
literal "true"
\end_inset
additionally the release of solvent from the aqua-complex involves an increase
in degrees of freedom in the system, which is energetically favorable due
to the increase of
\begin_inset ERT
status open
\begin_layout Plain Layout
\backslash
glslink{dS}{entropy change (
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textDelta
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textit{S})}
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.
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LatexCommand citep
key "Krezel2016"
literal "true"
\end_inset
\begin_inset ERT
status open
\begin_layout Plain Layout
\backslash
Glspl{mprotein}
\end_layout
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that utilize this unique
\begin_inset ERT
status open
\begin_layout Plain Layout
\backslash
gls{cofactor}
\end_layout
\end_inset
, are unique as well, and bind this metal ion in an unusual fashion.
\end_layout
\begin_layout Section
zinc-binding Sites
\begin_inset CommandInset label
LatexCommand label
name "sec:Zinc-Binding-Sites"
\end_inset
\end_layout
\begin_layout Standard
Zinc(II) binding proteins are extremely diverse in structure and function.
Zn(II) is an intermediate Lewis acid in terms of hardness according to
the
\begin_inset ERT
status open
\begin_layout Plain Layout
\backslash
gls{hsab}
\end_layout
\end_inset
, theory formulated by Ralph Pearson.
\begin_inset CommandInset citation
LatexCommand citep
key "Pearson1963"
literal "true"
\end_inset
Because of this, Zn(II) can be coordinated by zarówno the sulfur atom of
the cysteine (a soft Lewis base), the nitrogen atom of the histidine (an
intermediate Lewis base), as well as by carboxyl anions derived from the
aspartates and glutamates (a hard Lewis base).
The most common
\begin_inset ERT
status open
\begin_layout Plain Layout
\backslash
gls{Lg}
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found in the zinc-binding sites is cysteine, followed by histidine and
acidic residues, i.e.
aspartic acid and glutamic acid
\begin_inset Foot
status open
\begin_layout Plain Layout
Those findings are based on the structural data from the
\begin_inset ERT
status open
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\backslash
gls{rcsb}
\end_layout
\end_inset
.
Just because there are structures of such
\begin_inset ERT
status open
\begin_layout Plain Layout
\backslash
glspl{mprotein}
\end_layout
\end_inset
does not necessarily mean that this is true in all existing zinc-binding
sites existing.
\end_layout
\end_inset
.
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LatexCommand citep
key "Laitaoja2013"
literal "true"
\end_inset
For zinc-binding sites,
\begin_inset ERT
status open
\begin_layout Plain Layout
\backslash
glspl{cn}
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ranging from two to seven were found in the literature
\begin_inset CommandInset citation
LatexCommand citep
key "Sousa2009,Andreini2011"
literal "true"
\end_inset
, however, di- and tricoordinate are zinc complexes are highly reactive,
meaning that the stable zinc-binding sites have
\begin_inset ERT
status open
\begin_layout Plain Layout
\backslash
gls{cn}
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\end_inset
at least equal four.
Thorough manual analysis performed by
\begin_inset CommandInset citation
LatexCommand cite
key "Laitaoja2013"
literal "true"
\end_inset
ruled out of physiological existence of zinc-binding sites of
\begin_inset ERT
status open
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\backslash
gls{cn}
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higher than seven.
\begin_inset CommandInset citation
LatexCommand citep
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The most common zinc-binding sites found in the
\begin_inset ERT
status open
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gls{rcsb}
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\end_inset
have
\begin_inset ERT
status open
\begin_layout Plain Layout
\backslash
gls{cn}
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=4, which corresponds to the tetrahedral geometry.
The low occurrence of zinc-binding sites with
\begin_inset ERT
status open
\begin_layout Plain Layout
\backslash
gls{cn}
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\end_inset
>4 is probably due to the small size of Zn(II) (~74
\begin_inset space \space{}
\end_inset
pm and ~88
\begin_inset space \space{}
\end_inset
pm for
\begin_inset ERT
status open
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gls{cn}
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=4 and
\begin_inset ERT
status open
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gls{cn}
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=6, respectively), which causes molecular repulsion between the
\begin_inset ERT
status open
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glspl{Lg}
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LatexCommand citep
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literal "true"
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.
The
\begin_inset ERT
status open
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\backslash
gls{cn}
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equal to two in zinc-binding sites is usually caused by the not-fully resolved
structure of zinc-binding site having higher
\begin_inset ERT
status open
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\backslash
gls{cn}
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(e.g.
structure of
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gls{pf}
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status open
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\backslash
gls{rad}
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zinc hook domain,
\begin_inset ERT
status open
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\backslash
gls{pdb}
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\begin_inset CommandInset href
LatexCommand href
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LatexCommand citep
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), likewise
\begin_inset ERT
status open
\begin_layout Plain Layout
\backslash
gls{cn}
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=3 in most cases is unresolved zinc-binding site with
\begin_inset ERT
status open
\begin_layout Plain Layout
\backslash
gls{cn}
\end_layout
\end_inset
=4, which is a very common situation in enzymatic zinc-binding sites, where
the missing, unresolved
\begin_inset ERT
status open
\begin_layout Plain Layout
\backslash
gls{Lg}
\end_layout
\end_inset
is often a water molecule.
The different number and types of
\begin_inset ERT
status open
\begin_layout Plain Layout
\backslash
glspl{Lg}
\end_layout
\end_inset
often translate into differences in the properties of the coordination
sphere and zinc-binding site formed.
\end_layout
\begin_layout Standard
The process of Zn(II) complexation by polypeptide often entails the formation
of a stable conformation.
The zinc-binding sites can exist as a pre-made arrangement of amino acids
in the space, where zinc-binding does not cause huge structural changes
in protein (usually in enzymes), however, the zinc-binding can promote
protein folding and formation of separate protein domains (e.g., zinc fingers),
this process is often in structural zinc sites.
\begin_inset CommandInset citation
LatexCommand citep
key "Kochanczyk2015a"
literal "true"
\end_inset
\end_layout
\begin_layout Standard
Zinc-binding sites can be divided by function but also by their architecture.
Functionally, zinc sites can be divided into:
\end_layout
\begin_layout Standard
\begin_inset Flex CT - Description Label
status open
\begin_layout Plain Layout
\begin_inset Flex CT - Spaced Low Small Caps
status open
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catalytic
\end_layout
\end_inset
\end_layout
\end_inset
Zn(II) can be found in the active center of any of the six classes of enzymes
distinguished by the International Union of Biochemistry and Molecular
Biology.
In almost every enzyme Zn(II) acts as a
\begin_inset ERT
status open
\begin_layout Plain Layout
\backslash
gls{cofactor}
\end_layout
\end_inset
and one of the zinc
\begin_inset ERT
status open
\begin_layout Plain Layout
\backslash
glspl{Lg}
\end_layout
\end_inset
is a water molecule.
In other proteins with no catalytic function, Zn(II) is usually bound by
the atoms of the side chains of the amino acid residues.
The interaction of the water molecule with the zinc cation allows for the
transient replacement of the water molecule by the coordination of the
substrate molecule.
However in the case of the most studied carbonic anhydrase,
\begin_inset ERT
status open
\begin_layout Plain Layout
\backslash
glsfirst{ca2}
\end_layout
\end_inset
, the water molecule is not replaced displaced from the zinc-binding site,
Zn(II) lowers the water p
\begin_inset ERT
status open
\begin_layout Plain Layout
\backslash
gshort{Ka}
\end_layout
\end_inset
, facilitating dissociation to a hydroxide, that reacts with
\begin_inset ERT
status open
\begin_layout Plain Layout
\backslash
ce{CO2}
\end_layout