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Data collection, processing, structure solution, model building and

CHAPTER 4 STRUCTURE OF αGlyBP……………………………………... 73-123

4.2 MATERIALS AND METHODS

4.2.4 Data collection, processing, structure solution, model building and

4.2.4 Data collection, processing, structure solution, model building and

checked and validated by programs PROCHECK (Laskowski et al., 1993) and MolProbity (Chen et al., 2010). The three-dimensional atomic coordinates and the structure factors of all the structures have been deposited in the RCSB Protein Data Bank (Berman et al., 2000) with accession codes 6J9W, 6J9Y, 6JAD, 6JAG, 6JAH, 6JAI, 6JAL, 6JAM, 6JAN, 6JAO, 6JAP, 6JAQ, 6JAR, 6JAZ, 6JB0, 6JB4, 6JBA, 6JBB and 6JBE for αGlyBP_WT•TRE, αGlyBP_WT•MAL, αGlyBP_WT•PAL, αGlyBP_WT•SUC, αGlyBP_WT•GLC, αGlyBP_D118A•MAL, αGlyBP_R356A,

αGlyBP_R356A•TRE, αGlyBP_R356A•MAL, αGlyBP_R356A•PAL,

αGlyBP_R356A•SUC, αGlyBP_R356A•GLC, αGlyBP_R49A•MAL,

αGlyBP_W287F•TRE, αGlyBP_W287A•TRE, αGlyBP_W287A•MAL,

αGlyBP_W287A•PAL, αGlyBP_W287A•SUC and αGlyBP_W287A•GLC, respectively. All the molecular graphics figures of protein structures were prepared using PyMOL (Molecular Graphics System, Version 1.7.2.2 Schrödinger, LLC).

Table 4.2. Data collection and refinement statistics of αGlyBP_WT protein (bound to trehalose, maltose and palatinose). The values in parenthesis are for the last resolution shell.

αGlyBP WT•TRE αGlyBP WTMAL αGlyBP WTPAL

Wavelength (Å) 1.5418 1.5418 1.5418

Temperature

(K) 100 100 100

Space group P41212 P41212 P41212

Unit-cell parameters (Å, ᵒ)

a=b=84.91, c=145.80, α=β=γ=90

a=b=85.24, c=145.68, α=β=γ=90

a=b=84.77, c=145.83, α=β=γ=90 Resolution (Å) 48.60-1.80 (1.84-

1.80)

46.44-1.63 (1.66- 1.63)

59.94-1.90 (1.94- 1.90) No. of observed

reflections 611481 (35139) 611875 (26380) 279983 (18724) No. of unique

reflections 50048 (2860) 67774 (3302) 42666 (2695) Mn(I) CC(1/2) 0.999 (0.954) 0.998 (0.970) 0.997 (0.915) Completeness

(%) 99.8 (98.9) 100 (99.9) 99.9 (99.6)

VM 3 Da-1) 2.90 2.92 2.89

Solvent content

(%) 57.63 57.93 57.50

Mosaicity (°) 0.461 0.422 0.639

MeanI/σ(I) 18.8 (5.8) 18.5 (5.5) 13.2 (3.6)

Rmerge(%) 0.088 (0.435) 0.067 (0.242) 0.083 (0.449)

Rpim (%) 0.037 (0.185) 0.033 (0.135) 0.050 (0.268) Rmeas (%) 0.095 (0.473) 0.075 (0.278) 0.097 (0.524)

Multiplicity 12.2 (12.3) 9.0 (8.0) 6.6 (6.9)

Rwork/Rfree (%) 13.25/16.41 13.69/16.27 13.94/18.16

Protein model No. of subunits

in ASU 1 1 1

Protein atoms 3242 3274 3250

Water molecules 533 575 517

Trehalose 1 - -

Maltose - 1 -

Palatinose - - 1

Others 2 3 2

Deviation from ideal geometry

Bond length (Å) 0.020 0.022 0.018

Bond angles (°) 1.848 2.057 1.804

Average B-factor (Å2)

Protein atoms 16.73 16.19 21.60

Water

molecules 30.60 31.05 34.18

Trehalose 11.56 - -

Maltose - 11.88 -

Palatinose - - 15.75

Ramachandran plot

Favored (%) 97.73 98.47 98.49

Allowed (%) 1.77 1.27 1.26

Remaining (%) 0.51 0.25 0.25

PDB id 6J9W 6J9Y 6JAD

Rmerge = ∑hkl i|Ii(hkl) - 〈I(hkl)〉|/ ∑hkliIi(hkl), where I(hkl) is the intensity of reflection hkl, ∑hkl is the sum overall reflections and ∑i is the sum over i measurements of reflection hkl.

TRE: Trehalose; MAL: Maltose; PAL: Palatinose

Table 4.3. Data collection and refinement statistics of αGlyBP_WT (bound to sucrose and glucose) and αGlyBP_D118A mutant protein (bound to maltose). The values in parenthesis are for the last resolution shell.

αGlyBP WTSUC αGlyBP WTGLC αGlyBP D118A•M AL

Wavelength (Å) 1.5418 1.5418 1.5418

Temperature

(K) 100 100 100

Space group P41212 P41212 P41212

Unit-cell parameters (Å, ᵒ)

a=b=84.93, c=145.95, α=β=γ=90

a=b= 84.23, c=145.90, α=β=γ=90

a=b= 84.72, c=146.02, α=β=γ=90 Resolution (Å) 60.05-1.85 (1.89-

1.85)

48.63-1.63 (1.66- 1.63)

59.91-2.10 (2.16- 2.10) No. of observed

reflections 823750 (47317) 1181510 (51925) 493303 (38585) No. of unique

reflections 46411 (2826) 66385 (3266) 31860 (2553) Mn(I) CC(1/2) 0.999 (0.944) 0.999 (0.929) 0.998 (0.957) Completeness

(%) 100 (100) 100 (100) 100 (100)

VM 3 Da-1) 2.91 2.86 2.89

Solvent content

(%) 57.70 56.98 57.51

Mosaicity (°) 0.573 0.521 0.730

Mean I/σ(I) 24.3 (5.8) 22.3 (4.3) 17.5 (6.0)

Rmerge(%) 0.107 (0.573) 0.082 (0.647) 0.126 (0.481)

Rpim (%) 0.036 (0.203) 0.028 (0.239) 0.046 (0.180) Rmeas (%) 0.113 (0.608) 0.087 (0.690) 0.134 (0.514) Multiplicity 17.7 (16.7) 17.8 (15.9) 15.5 (15.1)

Rwork/Rfree (%) 12.93/16.68 13.48/16.05 14.17/18.99

Protein model No. of subunits

in ASU 1 1 1

Protein atoms 3255 3258 3246

Water

molecules 570 580 448

Sucrose 1 - -

Glucose - 1 -

Maltose - - 1

Calcium ion - - 1

Others 2 7 3

Deviation from ideal geometry

Bond length (Å) 0.019 0.021 0.017

Bond angles (°) 1.801 1.990 1.705

Average B-factor (Å2)

Protein atoms 14.93 17.28 20.22

Water

molecules 28.80 32.41 31.35

Sucrose 8.12 - -

Glucose - 10.12 -

Maltose - - 21.46

Calcium ion - - 18.07

Ramachandran plot

Favored (%) 97.73 97.73 97.78

Allowed (%) 1.77 1.77 1.51

Remaining (%) 0.51 0.51 0.50

PDB id 6JAG 6JAH 6JAI

Rmerge = ∑hkl i|Ii(hkl) - 〈I(hkl)〉|/ ∑hkliIi(hkl), where I(hkl) is the intensity of reflection hkl, ∑hkl is the sum overall reflections and ∑i is the sum over i measurements of reflection hkl.

SUC: Sucrose; GLC: Glucose

Table 4.4. Data collection and refinement statistics of αGlyBP_R356A mutant protein in open and closed conformation (bound to trehalose and maltose). The values in parenthesis are for the last resolution shell.

αGlyBP R356A αGlyBP R356ATRE αGlyBP R356AM AL

Wavelength

(Å) 1.5418 1.5418 1.5418

Temperature

(K) 100 100 100

Space group P21 P41212 P41212

Unit-cell parameters (Å, ᵒ)

a= 53.04, b=

85.13, c=55.34, α=γ=90, β=92.99

a=b=85.07, c=146.38, α=β=γ=90

a=b=84.41, c=145.55, α=β=γ=90 Resolution (Å) 44.97-1.56 (1.59-

1.56) 48.79-1.63 (1.66-1.63) 59.69-1.77 (1.81- 1.77) No. of

observed

reflections 318860 (14055) 1241773 (53313) 771334 (40657) No. of unique

reflections 69683 (3351) 67875 (3277) 49679 (2550) Mn(I) CC(1/2) 0.999 (0.994) 0.999 (0.953) 0.999 (0.967) Completeness

(%) 99.8 (96.4) 100 (100) 96.0 (87.8)

VM 3 Da-1) 2.76 2.92 2.86

Solvent content

(%) 55.39 57.96 57.06

Mosaicity (°) 0.357 0.542 0.559

Mean I/σ(I) 30.1 (15.0) 22.1 (4.6) 22.1 (6.2)

Rmerge(%) 0.031 (0.061) 0.078 (0.532) 0.083 (0.389)

Rpim (%) 0.024 (0.048) 0.026 (0.194) 0.029 (0.137) Rmeas (%) 0.040 (0.077) 0.082 (0.567) 0.089 (0.413)

Multiplicity 4.6 (4.2) 18.3 (16.3) 15.5 (15.9)

Rwork/Rfree (%) 12.71/15.05 13.81/16.59 13.25/16.35

Protein model No. of subunits

in ASU 1 1 1

Protein atoms 3396 3279 3251

Water

molecules 666 587 528

Trehalose - 1 -

Maltose - - 1

Others 7 6 7

Deviation from ideal geometry Bond length

(Å) 0.022 0.021 0.019

Bond angles (°) 2.155 1.955 1.856

Average B-factor (Å2)

Protein atoms 10.39 18.23 16.50

Water

molecules 25.21 32.83 30.50

Trehalose - 12.59 -

Maltose - - 10.52

Ramachandran plot

Favored (%) 98.75 97.73 97.98

Allowed (%) 1.00 1.77 1.77

Remaining (%) 0.25 0.51 0.25

PDB id 6JAL 6JAM 6JAN

Rmerge = ∑hkl i|Ii(hkl) - 〈I(hkl)〉|/ ∑hkliIi(hkl), where I(hkl) is the intensity of reflection hkl, ∑hkl is the sum overall reflections and ∑i is the sum over i measurements of reflection hkl.

TRE: Trehalose; MAL: Maltose

Table 4.5. Data collection and refinement statistics of αGlyBP_R356A mutant protein in closed conformation (bound to palatinose, sucrose and glucose). The values in parenthesis are for the last resolution shell.

αGlyBP R356APAL αGlyBP R356ASU C

αGlyBP R356A

GLC

Wavelength (Å) 1.5418 1.5418 1.5418

Temperature

(K) 100 100 100

Space group P41212 P41212 P41212

Unit-cell parameters (Å, ᵒ)

a=b=85.42, c=146.15, α=β=γ=90

a=b= 85.41, c=146.29, α=β=γ=90

a=b=84.62, c=146.23, α=β=γ=90

Resolution (Å) 60.40-1.77 (1.81-1.77) 60.39-1.77 (1.81- 1.77)

59.84-1.95 (2.00- 1.95) No. of observed

reflections 940791 (48057) 911320 (46820) 580422 (40079) No. of unique

reflections 53234 (2987) 53038 (2950) 39565 (2725) Mn(I) CC(1/2) 0.999 (0.982) 0.999 (0.986) 0.999 (0.952) Completeness

(%) 100 (100) 99.7 (98.6) 100 (100)

VM 3 Da-1) 2.94 2.95 2.89

Solvent content

(%) 58.24 58.27 57.47

Mosaicity (°) 0.481 0.421 0.388

Mean I/σ(I) 24.0 (6.1) 31.2 (8.8) 22.2 (6.0)

Rmerge(%) 0.080 (0.302) 0.063 (0.247) 0.108 (0.483)

Rpim (%) 0.027 (0.111) 0.022 (0.090) 0.041 (0.185) Rmeas (%) 0.085 (0.322) 0.067 (0.263) 0.116 (0.517)

Multiplicity 17.7 (16.1) 17.2 (15.9) 14.7 (14.7)

Rwork/Rfree (%) 15.49/19.94 15.04/19.53 13.14/16.71

Protein model No. of subunits

in ASU 1 1 1

Protein atoms 3273 3274 3247

Water molecules 557 556 531

Palatinose 1 - -

Sucrose - 1 -

Glucose - - 1

Others 4 3 5

Deviation from ideal geometry

Bond length (Å) 0.018 0.018 0.019

Bond angles (°) 1.827 1.799 1.783

Average B-factor (Å2)

Protein atoms 19.91 17.81 15.49

Water

molecules 34.33 32.16 28.71

Palatinose 12.68 - -

Sucrose - 10.13 -

Glucose - - 8.79

Ramachandran plot

Favored (%) 98.47 97.96 97.97

Allowed (%) 1.27 1.53 1.52

Remaining (%) 0.25 0.51 0.51

PDB id 6JAO 6JAP 6JAQ

Rmerge = ∑hkl i|Ii(hkl) - 〈I(hkl)〉|/ ∑hkliIi(hkl), where I(hkl) is the intensity of reflection hkl, ∑hkl is the sum overall reflections and ∑i is the sum over i measurements of reflection hkl.

PAL: Palatinose; SUC: Sucrose; GLC: Glucose

Table 4.6. Data collection and refinement statistics of αGlyBP_R49A (bound to maltose), αGlyBP_W287F and αGlyBP_W287A mutant proteins (bound to trehalose).

The values in parenthesis are for the last resolution shell.

αGlyBP R49AMA L

αGlyBP W287FTR E

αGlyBP W287ATR E

Wavelength

(Å) 1.5418 1.5418 1.5418

Temperature

(K) 100 100 100

Space group P41212 P41212 P41212

Unit-cell parameters (Å, ᵒ)

a=b=84.98, c=145.46, α=β=γ=90

a=b=85.27,

c=145.65, α=β=γ=90 a=b=84.76, c=146.21, α=β=γ=90 Resolution

(Å)

48.49-1.63 (1.66- 1.63)

48.55-1.85 (1.89- 1.85)

48.74-1.63 (1.66- 1.63) No. of

observed reflections

1006044 (44383) 690786 (41102) 804773 (35559) No. of

unique

reflections 61325 (2721) 46653 (2839) 65184 (2980) Mn(I)

CC(1/2) 0.999 (0.954) 0.999 (0.949) 0.999 (0.942) Completenes

s (%) 91.3 (83.4) 100 (99.9) 96.9 (91.5)

VM 3 Da-1) 2.90 2.92 2.90

Solvent

content (%) 57.61 57.95 57.61

Mosaicity

(°) 0.558 0.370 0.332

Mean I/σ(I) 24.3 (5.1) 21.6 (5.8) 24.4 (5.7)

Rmerge(%) 0.064 (0.391) 0.092 (0.511) 0.061 (0.381)

Rpim (%) 0.022 (0.139) 0.035 (0.196) 0.025 (0.160) Rmeas (%) 0.068 (0.416) 0.098 (0.547) 0.066 (0.414) Multiplicity 16.4 (16.3) 14.8 (14.5) 12.3 (11.9) Rwork/Rfree

(%) 13.99/16.62 13.26/16.83 13.42/16.02

Protein model

No. of subunits in

ASU 1 1 1

Protein

atoms 3262 3232 3249

Water

molecules 601 539 620

Maltose 1 - -

Trehalose - 1 1

Others 3 2 4

Deviation from ideal geometry Bond length

(Å) 0.020 0.019 0.020

Bond angles

(°) 1.932 1.835 1.947

Average B-factor (Å2) Protein

atoms 17.85 17.06 14.81

Water

molecules 33.00 30.34 30.05

Maltose 17.93 - -

Trehalose - 18.36 9.46

Ramachandran plot

Favored (%) 97.96 97.97 97.73

Allowed (%) 1.53 1.52 1.77

Remaining

(%) 0.51 0.51 0.51

PDB id 6JAR 6JAZ 6JB0

Rmerge = ∑hkl i|Ii(hkl) - 〈I(hkl)〉|/ ∑hkliIi(hkl), where I(hkl) is the intensity of reflection hkl, ∑hkl is the sum overall reflections and ∑i is the sum over i measurements of reflection hkl.

TRE: Trehalose

Table 4.7. Data collection and refinement statistics of αGlyBP_W287A mutant protein (bound to maltose, palatinose and sucrose). The values in parenthesis are for the last resolution shell.

αGlyBP W287AMA L

αGlyBP W287AP AL

αGlyBP W287A

SUC Wavelength

(Å) 1.5418 1.5418 1.5418

Temperature

(K) 100 100 100

Space group P41212 P41212 P41212

Unit-cell parameters (Å, ᵒ)

a=b=85.13, c=145.54, α=β=γ=90

a=b=84.10, c=146.02, α=β=γ=90

a=b=84.48, c=145.93, α=β=γ=90 Resolution

(Å) 48.51-1.63 (1.66-1.63) 59.47-2.00 (2.05- 2.00)

59.74-1.95 (2.00- 1.95) No. of

observed reflections

628881 (27856) 308917 (22315) 311670 (20698) No. of unique

reflections 67595 (3297) 36237 (2647) 38891 (2614) Mn(I)

CC(1/2) 0.999 (0.891) 0.990 (0.917) 0.997 (0.869) Completeness

(%) 100 (100) 100 (100) 99.0 (96.9)

VM 3 Da-1) 2.91 2.85 2.87

Solvent

content (%) 57.78 56.88 57.24

Mosaicity (°) 0.400 0.60 0.590

Mean I/σ(I) 17.1 (3.9) 10.4 (3.4) 13.4 (3.2)

Rmerge(%) 0.074 (0.457) 0.140 (0.574) 0.118 (0.557)

Rpim (%) 0.037 (0.246) 0.073 (0.308) 0.061 (0.285) Rmeas (%) 0.082 (0.520) 0.158 (0.653) 0.133 (0.629)

Multiplicity 9.3 (8.4) 8.5 (8.4) 8.0 (7.9)

Rwork/Rfree (%) 13.68/16.17 15.06/18.63 14.27/17.69

Protein model No. of

subunits in ASU

1 1 1

Protein atoms 3246 3254 3241

Water

molecules 593 448 473

Maltose 1 - -

Palatinose - 1 -

Sucrose - - 1

Others 5 4 5

Deviation from ideal geometry Bond length

(Å) 0.020 0.017 0.017

Bond angles

(°) 1.876 1.787 1.796

Average B-factor (Å2)

Protein atoms 16.13 22.37 18.07

Water

molecules 30.57 33.84 30.21

Maltose 11.31 - -

Palatinose - 20.84 -

Sucrose - - 10.82

Ramachandran plot

Favored (%) 97.73 97.72 97.48

Allowed (%) 1.77 1.77 2.02

Remaining

(%) 0.51 0.51 0.50

PDB id 6JB4 6JBA 6JBB

Rmerge = ∑hkl i|Ii(hkl) - 〈I(hkl)〉|/ ∑hkliIi(hkl), where I(hkl) is the intensity of reflection hkl, ∑hkl is the sum overall reflections and ∑i is the sum over i measurements of reflection hkl.

MAL: Maltose; PAL: Palatinose; SUC: Sucrose

Table 4.8. Data collection and refinement statistics of αGlyBP_W287A mutant protein (bound to glucose). The values in parenthesis are for the last resolution shell.

αGlyBP_W287AGLC

Wavelength (Å) 1.5418

Temperature (K) 100

Space group P41212

Unit-cell parameters (Å, ᵒ) a=b=84.99, c=145.83, α=β=γ=90

Resolution (Å) 55.56-1.75 (1.78-1.75)

No. of observed reflections 645449 (32906)

No. of unique reflections 52985 (2590)

Mn(I) CC(1/2) 0.999 (0.918)

Completeness (%) 97.0 (88.3)

VM 3 Da-1) 2.91

Solvent content (%) 57.72

Mosaicity (°) 0.448

Mean I/σ(I) 17.4 (3.9)

Rmerge(%) 0.092 (0.606)

Rpim (%) 0.037 (0.238)

Rmeas (%) 0.099 (0.652)

Multiplicity 12.2 (12.7)

Rwork/Rfree (%) 13.89/17.57

Protein model

No. of subunits in ASU 1

Protein atoms 3246

Water molecules 573

Glucose 1

Others 6

Deviation from ideal geometry

Bond length (Å) 0.018

Bond angles (°) 1.770 Average B-factor (Å2)

Protein atoms 18.64

Water molecules 32.31

Glucose 10.92

Ramachandran plot

Favored (%) 97.73

Allowed (%) 1.77

Remaining (%) 0.51

PDB id 6JBE

Rmerge = ∑hkl i|Ii(hkl) - 〈I(hkl)〉|/ ∑hkliIi(hkl), where I(hkl) is the intensity of reflection hkl, ∑hkl is the sum overall reflections and ∑i is the sum over i measurements of reflection hkl.

GLC: Glucose