-
Notifications
You must be signed in to change notification settings - Fork 0
/
Copy pathChapter02.lyx
2058 lines (1395 loc) · 30.4 KB
/
Chapter02.lyx
1
2
3
4
5
6
7
8
9
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
61
62
63
64
65
66
67
68
69
70
71
72
73
74
75
76
77
78
79
80
81
82
83
84
85
86
87
88
89
90
91
92
93
94
95
96
97
98
99
100
101
102
103
104
105
106
107
108
109
110
111
112
113
114
115
116
117
118
119
120
121
122
123
124
125
126
127
128
129
130
131
132
133
134
135
136
137
138
139
140
141
142
143
144
145
146
147
148
149
150
151
152
153
154
155
156
157
158
159
160
161
162
163
164
165
166
167
168
169
170
171
172
173
174
175
176
177
178
179
180
181
182
183
184
185
186
187
188
189
190
191
192
193
194
195
196
197
198
199
200
201
202
203
204
205
206
207
208
209
210
211
212
213
214
215
216
217
218
219
220
221
222
223
224
225
226
227
228
229
230
231
232
233
234
235
236
237
238
239
240
241
242
243
244
245
246
247
248
249
250
251
252
253
254
255
256
257
258
259
260
261
262
263
264
265
266
267
268
269
270
271
272
273
274
275
276
277
278
279
280
281
282
283
284
285
286
287
288
289
290
291
292
293
294
295
296
297
298
299
300
301
302
303
304
305
306
307
308
309
310
311
312
313
314
315
316
317
318
319
320
321
322
323
324
325
326
327
328
329
330
331
332
333
334
335
336
337
338
339
340
341
342
343
344
345
346
347
348
349
350
351
352
353
354
355
356
357
358
359
360
361
362
363
364
365
366
367
368
369
370
371
372
373
374
375
376
377
378
379
380
381
382
383
384
385
386
387
388
389
390
391
392
393
394
395
396
397
398
399
400
401
402
403
404
405
406
407
408
409
410
411
412
413
414
415
416
417
418
419
420
421
422
423
424
425
426
427
428
429
430
431
432
433
434
435
436
437
438
439
440
441
442
443
444
445
446
447
448
449
450
451
452
453
454
455
456
457
458
459
460
461
462
463
464
465
466
467
468
469
470
471
472
473
474
475
476
477
478
479
480
481
482
483
484
485
486
487
488
489
490
491
492
493
494
495
496
497
498
499
500
501
502
503
504
505
506
507
508
509
510
511
512
513
514
515
516
517
518
519
520
521
522
523
524
525
526
527
528
529
530
531
532
533
534
535
536
537
538
539
540
541
542
543
544
545
546
547
548
549
550
551
552
553
554
555
556
557
558
559
560
561
562
563
564
565
566
567
568
569
570
571
572
573
574
575
576
577
578
579
580
581
582
583
584
585
586
587
588
589
590
591
592
593
594
595
596
597
598
599
600
601
602
603
604
605
606
607
608
609
610
611
612
613
614
615
616
617
618
619
620
621
622
623
624
625
626
627
628
629
630
631
632
633
634
635
636
637
638
639
640
641
642
643
644
645
646
647
648
649
650
651
652
653
654
655
656
657
658
659
660
661
662
663
664
665
666
667
668
669
670
671
672
673
674
675
676
677
678
679
680
681
682
683
684
685
686
687
688
689
690
691
692
693
694
695
696
697
698
699
700
701
702
703
704
705
706
707
708
709
710
711
712
713
714
715
716
717
718
719
720
721
722
723
724
725
726
727
728
729
730
731
732
733
734
735
736
737
738
739
740
741
742
743
744
745
746
747
748
749
750
751
752
753
754
755
756
757
758
759
760
761
762
763
764
765
766
767
768
769
770
771
772
773
774
775
776
777
778
779
780
781
782
783
784
785
786
787
788
789
790
791
792
793
794
795
796
797
798
799
800
801
802
803
804
805
806
807
808
809
810
811
812
813
814
815
816
817
818
819
820
821
822
823
824
825
826
827
828
829
830
831
832
833
834
835
836
837
838
839
840
841
842
843
844
845
846
847
848
849
850
851
852
853
854
855
856
857
858
859
860
861
862
863
864
865
866
867
868
869
870
871
872
873
874
875
876
877
878
879
880
881
882
883
884
885
886
887
888
889
890
891
892
893
894
895
896
897
898
899
900
901
902
903
904
905
906
907
908
909
910
911
912
913
914
915
916
917
918
919
920
921
922
923
924
925
926
927
928
929
930
931
932
933
934
935
936
937
938
939
940
941
942
943
944
945
946
947
948
949
950
951
952
953
954
955
956
957
958
959
960
961
962
963
964
965
966
967
968
969
970
971
972
973
974
975
976
977
978
979
980
981
982
983
984
985
986
987
988
989
990
991
992
993
994
995
996
997
998
999
1000
#LyX 2.3 created this file. For more info see http://www.lyx.org/
\lyxformat 544
\begin_document
\begin_header
\save_transient_properties true
\origin unavailable
\textclass classicthesis
\begin_preamble
\usepackage{bohr}
\end_preamble
\use_default_options true
\maintain_unincluded_children false
\language american
\language_package default
\inputencoding utf8
\fontencoding global
\font_roman "default" "default"
\font_sans "default" "default"
\font_typewriter "default" "default"
\font_math "auto" "auto"
\font_default_family default
\use_non_tex_fonts false
\font_sc false
\font_osf false
\font_sf_scale 100 100
\font_tt_scale 100 100
\use_microtype false
\use_dash_ligatures true
\graphics default
\default_output_format default
\output_sync 0
\bibtex_command default
\index_command default
\paperfontsize default
\spacing single
\use_hyperref false
\papersize default
\use_geometry false
\use_package amsmath 1
\use_package amssymb 1
\use_package cancel 1
\use_package esint 0
\use_package mathdots 1
\use_package mathtools 1
\use_package mhchem 1
\use_package stackrel 1
\use_package stmaryrd 1
\use_package undertilde 1
\cite_engine biblatex
\cite_engine_type authoryear
\biblio_style plainnat
\biblatex_bibstyle numeric-comp
\biblatex_citestyle numeric-comp
\use_bibtopic false
\use_indices false
\paperorientation portrait
\suppress_date false
\justification true
\use_refstyle 0
\use_minted 0
\index Index
\shortcut idx
\color #008000
\end_index
\secnumdepth 2
\tocdepth 2
\paragraph_separation indent
\paragraph_indentation default
\is_math_indent 0
\math_numbering_side default
\quotes_style english
\dynamic_quotes 0
\papercolumns 1
\papersides 1
\paperpagestyle default
\tracking_changes false
\output_changes false
\html_math_output 0
\html_css_as_file 0
\html_be_strict false
\end_header
\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
\begin_layout Plain Layout
\begin_inset CommandInset ref
LatexCommand labelonly
reference "subsec:Transition-metal-ions"
plural "false"
caps "false"
noprefix "false"
\end_inset
\end_layout
\end_inset
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
\begin_inset CommandInset ref
LatexCommand labelonly
reference "fig:Bohr-model-diagram-zinc"
plural "false"
caps "false"
noprefix "false"
\end_inset
\end_layout
\end_inset
).
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
\begin_layout Plain Layout
\begin_inset CommandInset ref
LatexCommand labelonly
reference "fig:Bohr-model-diagram-zinc"
plural "false"
caps "false"
noprefix "false"
\end_inset
\end_layout
\end_inset
) – 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"
\end_inset
.
This limitation of Zn(II) being redox-inert in biology might produce a
false view of its use by evolution in proteins.
\end_layout
\begin_layout Standard
\begin_inset Float figure
wide false
sideways false
status open
\begin_layout Plain Layout
\begin_inset ERT
status open
\begin_layout Plain Layout
\backslash
setbohr{shell-options-add = dashed,
\end_layout
\begin_layout Plain Layout
distribution-method=quantum,
\end_layout
\begin_layout Plain Layout
insert-missing}
\end_layout
\begin_layout Plain Layout
\backslash
centering
\end_layout
\begin_layout Plain Layout
\backslash
bohr{}{Zn}
\end_layout
\begin_layout Plain Layout
\backslash
\backslash
\end_layout
\begin_layout Plain Layout
\backslash
elconf{Zn}
\end_layout
\end_inset
\end_layout
\begin_layout Plain Layout
\begin_inset Caption Standard
\begin_layout Plain Layout
\begin_inset CommandInset label
LatexCommand label
name "fig:Bohr-model-diagram-zinc"
\end_inset
Bohr model diagram for of zinc.
\end_layout
\end_inset
\end_layout
\end_inset
\end_layout
\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
\end_inset
]
\begin_inset script superscript
\begin_layout Plain Layout
2+
\end_layout
\end_inset
) and as a tetrahedral [Zn(H
\begin_inset script subscript
\begin_layout Plain Layout
2
\end_layout
\end_inset
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 (
\backslash
textDelta
\backslash
textit{S})}
\end_layout
\end_inset
.
\begin_inset CommandInset citation
LatexCommand citep
key "Krezel2016"
literal "true"
\end_inset
\begin_inset ERT
status open
\begin_layout Plain Layout
\backslash
Glspl{mprotein}
\end_layout
\end_inset
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}
\end_layout
\end_inset
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
\begin_layout Plain Layout
\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
.
\begin_inset CommandInset citation
LatexCommand citep
key "Laitaoja2013"
literal "true"
\end_inset
For zinc-binding sites,
\begin_inset ERT
status open
\begin_layout Plain Layout
\backslash
glspl{cn}
\end_layout
\end_inset
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}
\end_layout
\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
\begin_layout Plain Layout
\backslash
gls{cn}
\end_layout
\end_inset
higher than seven.
\begin_inset CommandInset citation
LatexCommand citep
key "Laitaoja2013"
literal "true"
\end_inset
The most common zinc-binding sites found in the
\begin_inset ERT
status open
\begin_layout Plain Layout
\backslash
gls{rcsb}
\end_layout
\end_inset
have
\begin_inset ERT
status open
\begin_layout Plain Layout
\backslash
gls{cn}
\end_layout
\end_inset
=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}
\end_layout
\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
\begin_layout Plain Layout
\backslash
gls{cn}
\end_layout
\end_inset
=4 and
\begin_inset ERT
status open
\begin_layout Plain Layout
\backslash
gls{cn}
\end_layout
\end_inset
=6, respectively), which causes molecular repulsion between the
\begin_inset ERT
status open
\begin_layout Plain Layout
\backslash
glspl{Lg}
\end_layout
\end_inset
\begin_inset CommandInset citation
LatexCommand citep
key "Miessler2013"
literal "true"
\end_inset
.
The
\begin_inset ERT
status open
\begin_layout Plain Layout
\backslash
gls{cn}
\end_layout
\end_inset
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
\begin_layout Plain Layout
\backslash
gls{cn}
\end_layout
\end_inset
(e.g.
structure of
\begin_inset ERT
status open
\begin_layout Plain Layout
\backslash
gls{pf}
\end_layout
\end_inset
\begin_inset ERT
status open
\begin_layout Plain Layout
\backslash
gls{rad}
\end_layout
\end_inset
zinc hook domain,
\begin_inset ERT
status open
\begin_layout Plain Layout
\backslash
gls{pdb}
\end_layout
\end_inset
\begin_inset CommandInset href
LatexCommand href
name "6ZFF"
target "https://www.rcsb.org/structure/6ZFF"
literal "false"
\end_inset
\begin_inset CommandInset citation
LatexCommand citep
key "Soh2021"
literal "true"
\end_inset
), likewise
\begin_inset ERT
status open
\begin_layout Plain Layout
\backslash
gls{cn}
\end_layout
\end_inset
=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
\begin_layout Plain Layout
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