Residues of Aspergillus niger Glucoamylase

Chemical and Site-Directed Modifications (Incomplete)


Region Pre-S1

Ala1 - conserved - Ser, Ala

- alpha-helix H1

Thr2 - conserved - Ala

- alpha-helix H1

Leu3 - conserved - Ile

- alpha-helix H1

Asp4 - not conserved - Glu, Ser

- alpha-helix H1

Ser5 - conserved - Glu

- alpha-helix H1

Trp6 - conserved

- not protected by acarbose N-bromosuccinimide

- alpha-helix H1

Leu7 - conserved - Ile

- alpha-helix H1

Ser8 - not conserved - Lys, Gln

- alpha-helix H1

Asn9 - not conserved - Lys, Arg

- alpha-helix H1

Glu10 - conserved - Gln, Glu

- not protected by acarbose EAC

- alpha-helix H1

Ala11 - not conserved - Glu, Lys

- alpha-helix H1

Thr12 - not conserved - Gly, Lys

- alpha-helix H1

Val13 - conserved - Ile

- alpha-helix H1

Ala14 - conserved - Ser

- alpha-helix H1

Arg15 - conserved - Ile

- alpha-helix H1

Thr16 - not conserved - Phe, Glu

- alpha-helix H1

Ala17 - conserved - Arg

- alpha-helix H1

Ile18 - conserved - Met

- alpha-helix H1

Leu19 - conserved - Phe

- alpha-helix H1

Asn20 - not conserved - Glu, Gln, Arg

- alpha-helix H1

Asn21 - conserved

- alpha-helix H1

Ile22 - conserved

- alpha-helix H1

Gly23 - conserved - Ala

- alpha-helix H1

Ala24 - not conserved - Tyr

Asp25 - conserved - Pro, Asp

- non-reacting group EAC

Gly26 - not conserved - Ser, Glu

Ala27 - conserved - Gly

Trp28 - not conserved - Val, Gln, Asn

- not protected by acarbose N-bromosuccinimide

Val29 - not conserved - Tyr, Phe, Pro

Ser30 - conserved - Pro, Ser, Asn

Gly31 - not conserved - Ser, Gly, Asn

Ala32 - not conserved - Ile, Gly, Ser

Asp33 - not conserved - Val, Leu, Ser, Ala

- non-reacting group EAC

Ser34 - conserved - Pro, Thr, Ser

Region S1

Gly35 - conserved

Ile36 - not conserved - Thr, Val, Phe

Val37 - conserved - Ile

Val38 - not conserved - Ile , Ala

Ala39 - conserved

...Sf... *Val39 - increase hydrophobicity

- same activity at 30deg. C

- no activity at 50deg. C

- no volumous groups accepted

...Sf... *Asp39 - decrease hydrophobicity

- no activity at 30deg. or 50deg. C

- no charged groups accepted

Ser40 - conserved

Pro41 - conserved - Leu

Ser42 - conserved

- H-bond carbonyl-O Asp44

Thr43 - conserved - Glu

Asp44 - not conserved - Ser, Thr, Ala

- non-reacting group EAC

- H-bond with sugar Asn395

Asn45 - not conserved - His, Gly, Asn

Pro46 - conserved

Asp47 - conserved

- not protected by acarbose EAC

- H-bond (3.4 Å) carbonyl-O Thr43

- H-bond (3.4 Å) Tyr95

- H-bond amide-N Phe49

...Sf... *Tyr47 - study of carboxyl group in S1

- no activity at 30deg. or 50deg. C

Tyr48 - conserved

- non-reacting group EAC

- H-bond Glu400

- H-bond Tyr311

- H-bond amide-N Phe48 ??

Phe49 - conserved - Tyr

Tyr50 - conserved

- non-reacting group EAC

- near Trp120

- H-bond (3.4 Å) carbonyl-O Asp47 ??

Thr51 - not conserved - Glu, Ala

Trp52 - conserved

- non-reacting group N-bromosuccinimide

- H-bond Glu179 (w/ Trp120 , Gln124)

- near Arg54, Asp176, ??

...Sf... *Arg52 - no activity at 30deg. or 50deg. C

...Sf... *Leu52 - no activity at 30deg. or 50deg. C

Thr53 - conserved - Ile

Arg54 - conserved

- H-bond Asp126

- H-bond Gln124

- H-bond Asp126 ??

- near Trp52 , Asp179

- alpha-helix H82

...Sf... *Lys54 - study of another basic residue

- no activity at 30deg. or 50deg. C

...Sf... *Thr54 - study of a polar but uncharged residue

- no activity at 30deg. or 50deg. C

Asp55 - conserved

- not protected by acarbose EAC

- cleft near Trp417

- interaction with Thr416 on free side of chain in active site ??

- alpha-helix H82

*Gly55 - decrease 22x in ko

- same Km

- selectivity data not available yet

...Sf... *Asn55 - no activity at 30deg. or 50deg. C

...Sf... *Tyr55 - no activity at 30deg. or 50deg. C

Ser56 - conserved - Ala

- alpha-helix H82

Gly57 - conserved - Ala , Gly

- alpha-helix H82

Leu58 - conserved - Ile

- alpha-helix H82

Val59 - conserved - Thr, Val

- alpha-helix H82

Region Inter S1 - S2

Leu60 - not conserved - Ile, Phe, Ser

- alpha-helix H82

Lys61 - conserved - Asn, Leu, Lys

- alpha-helix H82

Thr62 - not conserved - Thr, Ser, Val

- alpha-helix H82

- H-bond Asp65

Leu63 - conserved - Ile, Val, Leu

- alpha-helix H82

Val64 - conserved - Leu

- alpha-helix H82

Asp65 - not matched

- not protected by acarbose EAC

- alpha-helix H82

- H-bond Lys61

Leu66 - conserved - Ser, Tyr, Leu

- alpha-helix H82

Phe67 - not conserved - Glu, His

- alpha-helix H82

Arg68 - not conserved - Ser, Leu, Tyr

- alpha-helix H82

Asn69 - not conserved - Asn, Ala, Glu

- alpha-helix H82

Gly70 - not conserved - Gly, Asp, Thr

Asp71 - not conserved - Pro, Asn, Thr

- non-reacting group EAC

Thr72 - not conserved - Ala, Asn, Leu

- alpha-helix H83

Ser73 - not conserved - Ser, Ile, Phe

- alpha-helix H83

Leu74 - not conserved - Glu, Asn, Gly

- alpha-helix H83

Leu75 - not conserved - Thr, Asn

- alpha-helix H83

Ser76 - not conserved - Leu, Thr, Lys

- alpha-helix H83

Thr77 - conserved - Leu, Thr

- alpha-helix H83

Ile78 - not conserved - Ile, Gln, Val

- alpha-helix H83

Glu79 - conserved - Leu, Ile, Glu

- non-reacting group or not protected by acarbose EAC

- alpha-helix H83

Asn80 - conserved

- alpha-helix H83

Tyr81 - conserved - Val, Thr, Tyr

- non-reacting group EAC

- alpha-helix H83

Ile82 - conserved - Ser, Ile

- alpha-helix H83

Ser83 - not conserved - Phe, Tyr, Leu

- alpha-helix H83

Ala84 - not conserved - His, Asn, Lys

- alpha-helix H83

Gln85 - conserved - Leu, Gln, Asp

- alpha-helix H83

Ala86 - conserved - Glu, Ala, Tyr

- alpha-helix H83

Ile87 - conserved - Arg, Val, Ile

- alpha-helix H83

Val88 - conserved - Thr, Ser, Val

- alpha-helix H83

Gln89 - not conserved - Asn, Ser

- alpha-helix H83

Gly90 - conserved - Asn, Phe, Gly

- alpha-helix H83

Ile91 - not conserved - Thr, Pro, Ser

Ser92 - not conserved - Ser, Leu, Val

Asn93 - not conserved - Ala, Ser, Lys

Pro94 - not conserved - Gly, Phe, Thr

Ser95 - not conserved - Ile, Gln

Gly96 - conserved - Asp, Ser

Asp97 - not conserved - Asp, Tyr, Thr

- non-reacting group EAC

Leu98 - not conserved - Thr, Glu, Ser

Ser99 - conserved - Asn, Ser, Thr

Ser100 - not conserved - Asp, Val

Gly101 - not conserved - Thr, His, Cys

Ala102 - not conserved - Val, Lys, Asn

Gly103 - not conserved - Gly, Ala, Cys

Region S2

Leu104 - conserved

Gly105 - conserved

Glu106 - conserved - Asp

- not protected by acarbose EAC

Pro107 - conserved

Lys108 - conserved

- near Trp120

Phe109 - conserved - Trp

Asn110 - conserved

- far away - subsite 5 ??

Val111 - not conserved - Thr, Pro, Val

Asp112 - conserved

- non-reactive or in part protected by acarbose EAC

Glu113 - not conserved - Gly , Asn

- non-reacting group EAC

Thr114 - conserved - Ser

Ala115 - conserved - Gly

- conserved in alpha-amylases

Tyr116 - conserved - Phe

- conserved in alpha-amylases

- partial oxydation with N-bromosuccimidine when unprotected

- near Trp120

*Ala116 - decrease 2 to 7x of ko

- Km (moderate decrease for G2 + iG2, 3x for G7)

- decrease 2x selectivity of G7 over G2)

Thr117 - conserved

- conserved in alpha-amylases

Gly118 - conserved - Glu

- conserved in alpha-amylases

Ser119 - not conserved - Ala, Pro, Asp

- far away - subsite ??

*Tyr119 - slightly higher ko

- slightly smaller Km

- no selectivity data available yet

Trp120 - conserved

- protected by acarbose N-bromosuccinimide

- essential for activity

- located near subsite 4

- influences subsites 1 and 2

- H-bond Glu179 (w/ Trp52 , Gln124)

- near Trp50, Lys108, Trp116

*His120 - decrease 60 to 220x of ko

- Km (2x decrease for G2 , 1.5X increase for G7)

- increase 1.5x selectivity of G7 over G2

*Leu120 - decrease 46 to 56x of ko

- Km (3x decrease for G2)

- decrease 3x selectivity of G7 over G2

...Sf... *Leu120 - no activity at 30deg. or 50deg. C

*Phe120 - decrease 53 to 81x of ko

- Km (2x decrease for G2)

- small decrease of selectivity of G7 over G2

*Tyr120 - decrease 83 to 191x of ko

- Km (3x decrease for G2, 4x decrease for G7, 11x

decrease for iG2)

- small decrease of selectivity of G7 over G2

- decrease 6x selectivity of iG2 over G2

Gly121 - conserved

Arg122 - conserved

Pro123 - conserved

Gln124 - conserved

- H-bond Glu179 (w/ Trp52 , Trp120)

- H-bond Arg54

Arg125 - conserved - Asn, Arg

- H-bond Arg54 ??

Asp126 - conserved

- non-reacting group EAC

- H-bond Arg54 ??

- H-bond amide-N Gly126

Gly127 - conserved

Pro128 - conserved

- interaction Tyr165

Ala129 - conserved

Leu130 - conserved - Glu

- alpha-helix H84

Arg131 - conserved

- alpha-helix H84

Ala132 - conserved - Ser

- alpha-helix H84

Thr133 - not conserved - Thr, Ile, Tyr

- alpha-helix H84

Ala134 - conserved - Thr

- alpha-helix H84

Region Inter S2 - S3

Met135 - not conserved - Lys, Arg, Phe

- alpha-helix H84

Ile136 - conserved - Tyr

- alpha-helix H84

Gly137 - conserved - Ile, Leu, Gly

- alpha-helix H84

Phe138 - not conserved - Phe, Tyr, Glu

- alpha-helix H84

Gly139 - not conserved - Ile, Gly, Ala

- alpha-helix H84

Gln140 - not conserved - Lys, Gln, Asp

- alpha-helix H84

Trp141 - not conserved - Gln, Leu, Ser

- non-reacting group N-bromosuccinimide

- alpha-helix H84

Leu142 - not conserved - Ser, Tyr, Val

- alpha-helix H84

Leu143 - conserved - Gly

- alpha-helix H84

Asp144 - conserved - Thr, Asp

- alpha-helix H84

Asn145 - conserved - Asp, Asn, Gln

- alpha-helix H84

Gly146 - not conserved - Leu, Thr, Ser

Tyr147 - conserved - Gly, Tyr, Lys

- partial oxydation with N-bromosuccimidine when unprotected

Thr148 - not conserved - Asp, Ala

Ser149 - not conserved - Lys, Ile, Ala

- alpha-helix H85

Thr150 - not conserved - Tyr, Ser

- alpha-helix H85

Ala151 - not conserved - Pro, Tyr, Asn

- alpha-helix H85

Thr152 - not conserved - Thr, Gln, Ser

- alpha-helix H85

Asp153 - conserved - Ser, Asp, Gly

- in part protected by acarbose EAC

- alpha-helix H85

Ile154 - conserved - Thr, Ile

- alpha-helix H85

Val155 - not conserved - Ala, Leu, Glu

- alpha-helix H85

Trp156 - conserved - Asp, Trp, Lys

-non-reacting group N-bromosuccinimide

- alpha-helix H85

Pro157 - conserved - Ile, Pro

- alpha-helix H85

Leu158 - not conserved - Phe, Tyr, Ala

- alpha-helix H85

Val159 - not conserved - Glu, Ile, Lys

- alpha-helix H85

Arg160 - conserved - Phe, Lys

- alpha-helix H85

Asn161 - not conserved - Trp, Pro,Lys

- alpha-helix H85

Region S3

Asp162 - conserved

- non-reacting group EAC

- alpha-helix H85

Leu163 - conserved

- alpha-helix H85

Ser164 - not conserved - Arg, Glu , Asp

- alpha-helix H85

Tyr165 - conserved - Phe

- alpha-helix H85

- interaction Pro128

Val166 - conserved - Ile

- alpha-helix H85

Ala167 - conserved - Ile, Val, Ala

- alpha-helix H85

Gln168 - not conserved - Asp, Gly, Asn

- alpha-helix H85

Tyr169 - not conserved - Tyr, His, Val

- partial oxydation with N-bromosuccimidine when unprotected

Trp170 - conserved

- protected only with isomaltose N-bromosuccinimide

- H-bond Gln216

Asn171 - conserved - Ser, Asp

- N-glycosylation site

Gln172 - not conserved - Ser, Asn

Thr173 - not conserved - Thr, Ser, Gly

- essential for N-glycolysation

Gly174 - conserved - Cys

Tyr175 - conserved - Phe, Tyr

- partial oxydation with N-bromosuccimidine when unprotected

Asp176 - conserved

- protected by acarbose EAC

- catalytic base of pKa 2.7 located between subsites 1 and 2

- H-bond amide-N Glu180 ( important conformational role)

- H2O-bridges Ser185 ?? , Asp247 ??

- near Trp52 (Arg54, ??)

* Glu176 - activity observed

* Asn176 - decrease 10 to 20x in ko

- Km - increase 3 to 4x

- decreases 2x selectivity toward G2 over iG2

- increases 2x selectivity toward G6 over G2

aa176.5[*] - insertion based on homology with alpha-amylases

* Gly176.5 - no activity observed

* Asp176.5 - not studied yet

Leu177 - conserved

- affects binding to subsites 1 and 2 (+ Trp178 and Asn182)

- also expected to be involved in the Trp120 conformation

- fills space in cleft

* His177 - decrease ko (10x iG2 , 6x G2 + G6)

- increase KM ( 1.5x G6 + iG2 , 3x G2)

- no change in selectivity for G2/iG2

- increases 2x selectivity toward G6 over G2

* Asp177 - activity observed

- hydrophobic ring increases selectivity for G2 hydrolysis ??

* Phe177 and Trp177 planned

Trp178 - conserved

- not protected by acarbose N-bromosuccinimide

- bond with Arg241 (with Tyr306)

- H-bond with Asp245

- stacked with Arg305 (which is stacked with Trp317)

* Arg178 - based on a-amylase homology

- decrease 4 to 8x for ko

- Km (slight decrease G2 and increase G6 , 2x iG6)

- increased 2x selectivity toward G2 over iG2

- decreased 2x selectivity toward G6 over G2

* Asp178 - no activity observed

* His178 , Phe178 and Tyr178 planned (bulky side-chains)

Glu179 - conserved

- protected by acarbose EAC

- general acid catalyst with pKa 5.9

- H-bond Trp52

- H-bond Trp120

- H-bond Gln124

* Gln179 - decrease of ko 20x for G7

- Km (slight decrease for G7)

- no selectivity data

* Asp179 - no activity observed

Glu180 - conserved

- protected by acarbose EAC

- envolved in substrate binding -interacts with 2'- and 3'-OH of G2

- H-bond Arg305

- H-bond Tyr306

* Gln180 - decrease 2 to 10x for ko

- increase 3 to 4x for Km

- increased 2x selectivity toward G7 over G2

- decrease 30x selectivity toward G2 over iG2

* Asp180 - activity observed

Val181 - conserved - Asn

* Asp181 - activity observed

Asn182 - conserved - Gln

- H-bond carbonyl-O Gly174

* Ala182 - based on homology with a-amylase

- slight decrease for ko

??? - Km (slight decrease for G2, slight increase for G7,

2x increase for iG2)

- selectivity increase of G2 over iG2

* Asp182 - not studied yet

Gly183 - conserved

* Lys183 - slightly higher ko

- slightly smaller Km

- no selectivity data available yet

Ser184 - not conserved - Met, Val, Arg

- alpha-helix H86

?? * His184 - no kinetic data available

Ser185 - conserved - His, Ser

- alpha-helix H86

- H-bond Thr188

Phe186 - conserved

- near bottom of cleft

- alpha-helix H86

Phe187 - conserved - Tyr

- near bottom of cleft

- alpha-helix H86

Thr188 - conserved

- alpha-helix H86

- H-bond amide-N Gly174 ??

- H-bond Ser185

Ile189 - conserved - Leu, Ser, Ile

- alpha-helix H86

Ala190 - conserved - Leu, Met, Ala

- alpha-helix H86

Val191 - conserved

- alpha-helix H86

Gln192 - conserved - Met

- alpha-helix H86

His193 - not conserved - Leu, Gln, Arg

- non-reacting group EAC

- alpha-helix H86

Arg194 - not conserved - Lys, Ser

- alpha-helix H86

Ala195 - conserved - Gly

- alpha-helix H86

Leu196 - conserved - Val

- alpha-helix H86

Region Inter S3 - S4

Val197 - not conserved - Asp, Ala, Leu

- alpha-helix H86

Glu198 - not conserved - Tyr, Arg, Lys, Leu

- non-reacting group EAC

- alpha-helix H86

Gly199 - not conserved - Gly, Ser, Ala

- alpha-helix H86

Ser200 - not conserved - Leu, Val, Ala

- alpha-helix H86

Ala201 - not conserved - Asp, Ser

- alpha-helix H86

Phe202 - not conserved - Phe, Tyr, Ile

- alpha-helix H86

Ala203 - conserved - Phe

- alpha-helix H86

Thr204 - not conserved - Lys, Asn

- alpha-helix H86

Ala205 - conserved - Ser, Arg

- alpha-helix H86

Val206 - not conserved - Ser, Phe, Asn

- alpha-helix H86

Gly207 - not conserved - Gly, Glu, Asp

Ser208 - not conserved - Asp, Arg

Ser209 - conserved - Gly

Cys210 - not conserved - Ser, Asp, Thr

- S-bond with Cys213

- alpha-helix H87

Ser211 - not conserved - Pro, Phe, Arg

- alpha-helix H87

Trp212 - not conserved - Ala, Phe

- protected by acarbose, maltose and isomaltose N-bromosuccinimide

- alpha-helix H87

Cys213 - not conserved - Val, Asn, Ser

- S-bond with Cys210

- alpha-helix H87

Asp214 - not conserved - Thr, Glu

- non-reacting group EAC

- alpha-helix H87

Ser215 - conserved - Arg

- alpha-helix H87

Gln216 - conserved - Thr

- alpha-helix H87

- H-bond Trp170

Ala217 - conserved - Thr

- alpha-helix H87

Pro218 - not conserved - Ser, Arg

- alpha-helix H87

Glu219 - not conserved - Thr, Arg

- non-reacting group EAC

- alpha-helix H87

Ile220 - not conserved - Ile, Asp, Leu

- alpha-helix H87

Leu221 - not conserved - Ile, Glu, Ala

- alpha-helix H87

Cys222 - conserved - Ser, Asn, Cys

- S-bond with Cys449

- alpha-helix H87

Tyr223 - conserved - Arg, Tyr

- partial oxydation with N-bromosuccimidine when unprotected

- alpha-helix H87

Leu224 - not conserved - Leu, Phe, Ile

- alpha-helix H87

Gln225 - not conserved - Leu, Ser

- alpha-helix H87

Ser226 - conserved - Val

- alpha-helix H87

Phe227 - not conserved - Phe, Asp, Gly

- alpha-helix H87

Trp228 - not conserved - Trp, Pro, Ser

- non-reacting group

- alpha-helix H87

Thr229 - not conserved - Ala, Asp, Val

Gly230 - not conserved - Gly, Asn, Ser

Ser231 - conserved - Gly, Asp

Phe232 - conserved - Asn

Ile233 - conserved - Val, Asn

Leu234 - conserved - Asn, Leu, Trp

Ala235 - not conserved - Gly, Thr, Ile

Asn236 - not conserved - Arg, Asp, Gln

Phe237 - not conserved - Val, Tyr

Asp238 - conserved - Asn, Asp, Ser

- non-reacting group EAC

Ser239 - not conserved - Tyr, His, Gln

Ser240 - conserverd - Ile, Ser, Arg

Arg241 - conserved - Pro, Arg

- H-bond Glu180

- H-bond Tyr306

Ser242 - not conserved - Glu, Gly, Thr

- H-bond Glu308

Gly243 - not conserved - Gly, Thr, Asn

Lys244 - conserved - Pro, Gly, Lys

Asp245 - not conserved - Ser, Leu

- non-reacting group EAC

- in vicinity to be catalytic

- H-bonds to Trp178

Ala246 - conserved - Arg, Lys, Ala, Thr

- alpha-helix H8

Asn247 - not conserved - Ser, Gln, Lys

- alpha-helix H8

- close (< 5 Å) Asp176

Thr248 - conserved - Gly, Thr

- alpha-helix H8

Leu249 - conserved

- alpha-helix H8

Leu250 - conserved - Asp, Leu

- alpha-helix H8

Gly251 - not conserved - Ile, Ser,Val

- alpha-helix H8

Ser252 - conserved - Ala

- alpha-helix H8

Ile253 - conserved - Thr, Ile

- alpha-helix H8

His254 - conserved - Leu, Tyr, His

- iodoacetamide-modified

- behind Trp417 stabilization ?

- directing binding ?

- bottom of cleft ?

- alpha-helix H8

Thr255 - conserved - Leu, Thr, Ile

- alpha-helix H8

Phe256 - conserved - Ala, Phe, Gly

- alpha-helix H8

Asp257 - conserved - Ala, Asp, Pro

- non-reacting group EAC

Pro258 - conserved - Asn, Pro, Leu

Glu259 - conserved - His, Glu, Leu

- in part protected by acarbose EAC

Ala260 - conserved - Asp, Ala, Gly

Ala261 - conserved - Ile, Ser

Cys262 - not conserved - Pro, Gly, Val

- S-bond with Cys270

Asp263 - not conserved - Asp, Ser, Glu

- non-reacting group EAC

Asp264 - not conserved - Asp, Ala, Ser

- non-reacting group EAC

Ser265 - conserved - Gly

Thr266 - not conserved - His, Ser, Phe

- H-bond Glu439

Phe267 - not conserved - Phe, Leu, Thr

Gln268 - conserved - Pro, Thr, Gln

Pro269 - conserved - Phe, Pro

Cys270 - conserved - Asp, Cys, Gly

- S-bond with Cys262

Ser271 - conserved - Ser, Ile, Val

Pro272 - not conserved - Asn, Asp, Glu

- alpha-helix H9

Arg273 - not conserved - Asp, Asn, Lys

- alpha-helix H9

Ala274 - not conserved - Pro, Glu, Ile

- alpha-helix H9

Leu275 - not conserved - Leu, Ala, Tyr

- alpha-helix H9

Ala276 - conserved - Val, Ala

Asn277 - conserved - Leu, Asn, Thr

- alpha-helix H9

His278 - not conserved - Asn, Gln, Ala

- not protected by acarbose EAC

- alpha-helix H9

Lys279 - not conserved - Thr, Val, Ser

- alpha-helix H9

Glu280 - not conserved - Leu, Ala, Tyr

- non-reacting or not protected by acarbose EAC

- alpha-helix H9

Val281 - not conserved - Val, His, Tyr

- alpha-helix H9

Val282 - not conserved - His, Leu, Glu

- alpha-helix H9

Asp283 - conserved - Leu, Asp

- non-reacting group EAC

- alpha-helix H9

Ser284 - not conserved - Ser, Met, Leu

- alpha-helix H9

Phe285 - not conserved - Phe, Leu, Glu

- alpha-helix H9

Arg286 - conserved - Ala, Asp

- alpha-helix H9

- H-bond carbonyl-O Asp297 ??

- H-bond carbonyl-O Glu299 ??

Ser287 - conserved - Asn

- alpha-helix H9

Ile288 - conserved - Lys, Leu

- alpha-helix H9

Tyr289 - conserved - Asp

- non-reacting group EAC

- alpha-helix H9

Thr290 - conserved - Pro, Thr, Arg

- alpha-helix H9 ??

Leu291 - conserved - Ile, Leu, Tyr

- alpha-helix H9 ??

Asn292 - conserved - Ser

- alpha-helix H9 ??

Asp293 - conserved - Val, Arg

- non-reacting group EAC

- alpha-helix H9 ??

Gly294 - not conserved - Asn, Ser

- alpha-helix H9 ??

Leu295 - conserved - Ser, Leu

- alpha-helix H9 ??

Ser296 -not conserved - Lys, Ala, Pro

Asp297 - not conserved - Asn, Tyr, Ser

- non-reacting group EAC

Ser298 - not conserved - Ser, Ala, Tyr

Glu299 - not conserved - Thr, Ala, Leu

- non-reacting group EAC

Region S4

Ala300 - conserved - Gly, Ala

Val301 - not conserved - Ile, Ala, Asn

Ala302 - conserved - Ser

Val303 - not conserved - Ile, Leu

Gly304 - conserved

- rigid point

Arg305 - conserved

- 2 H-bonds Asp309

- H-bond Glu180

Tyr306 - conserved

- non-reacting-group EAC

- H-bond Glu180

- H-bond Arg241

* Phe306 - decrease 1.5x ko

- increase 2x Km

- no selectivity data yet

Pro307 - conserved

Glu308 - conserved

- non-reacting group EAC

- H-bond Ser242

Asp309 - conserved

- non-reacting group EAC

- 2 H-bonds Asp305

- H-bond Tyr311

* Asn309 - decrease 20x ko

- increase 4x Km

- no selectivity data yet

Thr310 - conserved - Val, Thr

Tyr311 - conserved

- non-reacting group EAC

- H-bond Tyr48

- H-bond Asp309

- cleft

Tyr312 - not conserved - Asn, Asp

- non-reacting group EAC

- cleft

Asn313 - not conserved - Asn, Tyr, Asp

Gly314 - conserved

Asn315 - conserved

- H-bond with Gln401 (structure stabilization ?)

Pro316 - conserved - Ser

Trp317 - conserved

- non-reacting group N-bromosuccinimide

- stacked with Arg305 (which is stacked with Trp178)

- stacked with Glu400 ??

Phe318 - conserved - Val

- alpha-helix H10

Leu319 - conserved

- alpha-helix H10

Cys320 - conserved - Ala , Cys

- alpha-helix H10

Region Inter S4 - S5

Thr321 - conserved - Val

- alpha-helix H10

Leu322 - not conserved - Thr, Ala, Tyr

- alpha-helix H10

Ala323 - conserved - Gly

- alpha-helix H10

Ala324 - not conserved - Ala, Ser, Tyr

- alpha-helix H10

Ala325 - not conserved - Ala, Thr, Gln

- alpha-helix H10

Glu326 - not conserved - Glu, Thr, Val

- alpha-helix H10

Gln327 - conserved - Lys

- alpha-helix H10

Leu328 - conserved

- alpha-helix H10

Tyr329 - conserved

- partial oxidation with N-bromosuccinimide when unprotected

- alpha-helix H10

Asp330 - conserved - Arg, Asp

- not protected by acarbose EAC

- alpha-helix H10

Ala331 - conserved - His

- alpha-helix H10

Leu332 - conserved - Ile, Lys, Leu

- alpha-helix H10

Tyr333 - conserved - Ser, Arg, Tyr

- non-reacting group EAC

- alpha-helix H10

Gln334 - conserved - Ser

- alpha-helix H10

Trp335 - not conserved - Trp, His, Asn

- non-reacting group N-bromosuccinimide

- alpha-helix H10

Asp336 - conserved - Ile

- non-reacting group EAC

- alpha-helix H10

Lys337 - not conserved - Leu, Ile, Gln

- alpha-helix H10

Gln338 - not conserved - Val, Asn

- alpha-helix H10

Gly339 - not conserved - Gly, Val

- beta-strand 1

Ser340 - not conserved - Pro, Thr, Gly

- beta-strand 1

Leu341 - not conserved - Met, Val, Ile

- beta-strand 1

Glu342 - conserved - Asn, Thr, Glu

- non-reacting group EAC

- beta-strand 1

Val343 - not conserved - Val, Asn, Lys

- beta-strand 1

Thr344 - not conserved - Asp, Ser

Asp345 - not conserved - Cys, Ser

- non-reacting group EAC

Val346 - not conserved - Ile, Ser

- alpha-helix H11

Ser347 - conserved - Asn, Ser

- alpha-helix H11

Leu348 - not conserved - Leu, Ala, Tyr

- alpha-helix H11

Asp349 - not conserved - Asp, Phe, Pro

- non-reacting group EAC

- alpha-helix H11

Phe350 - conserved - Trp

- alpha-helix H11

Phe351 - conserved - Ser

- alpha-helix H11

Lys352 - not conserved - Lys, Glu, Asn

- alpha-helix H11

Ala353 - not conserved - Lys, Leu

- alpha-helix H11

Leu354 - not conserved - Val, Tyr, Phe

- alpha-helix H11

Tyr355 - not conserved - Phe, Ile, Asp

- partial oxidation with N-bromosuccinimide when unprotected

- non-reacting group EAC

Ser356 - conserved - Val

Asp357 - not conserved - Asp, Asn, Ser

- non-reacting group EAC

Ala358 - conserved - Leu, Ala

Ala359 - conserved - Thr, Ser, Ala

Thr360 - conserved - Ser

Gly361 - not conserved - Gly, Leu, Ile

- beta-strand 1

Thr362 - not conserved - Thr, Asn, Lys

- beta-strand 1

Tyr363 - not conserved - Tyr, Asp, Ile

- partial oxidation with N-bromosuccinimide when unprotected

- non-reacting group EAC

- beta-strand 1

- H-bond carbonyl-O Ala359

Ser364 - not conserved - Glu, Lys, Thr

- beta-strand 1

Ser365 - not conserved - Ser, Gly, Val

- beta-strand 1

Ser366 - not conserved - Gly, Tyr

Ser367 - not conserved - Ser, Leu, Thr

Ser368 - not conserved - Ser, Ile

- alpha-helix H12

Thr369 - not conserved - Asp, Leu

- alpha-helix H12

Tyr370 - conserved - Glu, Tyr, Phe

- non-reacting group EAC

- alpha-helix H12

Ser 371 - conserved - Phe, Ser, Asn

- alpha-helix H12

Ser372 - conserved - Asn, Ser

- alpha-helix H12

Ile373 - conserved - Thr, Leu, Ile

- alpha-helix H12

Val374 - not conserved - Val, Pro, Ala

- alpha-helix H12

Asp375 - conserved - Ala, Gln, Asp

- not protected by acarbose EAC

- alpha-helix H12

Ala376 - not conserved - Phe, Asp, Asn, Ala

- alpha-helix H12

Val377 - conserved - Asn, Ile, Val

- alpha-helix H12

Lys378 - not conserved - Gln, Leu, Ala

- alpha-helix H12

Thr379 - conserved - Leu

- alpha-helix H12

Phe380 - not conserved - Phe, Ile, Ala

- alpha-helix H12

Ala381 - not conserved - Ala, Gln, Gly

- alpha-helix H12

Asp382 - conserved - Lys

- non-reacting group EAC

- alpha-helix H12

Gly383 - not conserved - Ile, Ser, Arg

- alpha-helix H12

Phe384 - conserved

- alpha-helix H12

Val385 - not conserved - Gln, Leu

- alpha-helix H12

Ser386 - conserved - Leu, Ser

- alpha-helix H12

Ile387 - not conserved - Ala, Gln, Thr

- alpha-helix H12

Val388 - conserved - Asp

- alpha-helix H12

Glu389 - not conserved - Ser, Gln, Ile

- in part protected by acarbose EAC

- alpha-helix H12

Thr390 - not conserved - Leu, Phe

- alpha-helix H12

His391 - conserved - Leu

- non-reacting group EAC

- alpha-helix H12

Ala392 - not conserved - Ala, Val, Ile

- alpha-helix H12

Ala393 - not conserved - Lys, Asn, His

Ser394 - not conserved - Leu, Asp, Asn

Asn395[ ] - not conserved - Asn, Lys[*], Asp

- N-glycosylation site

- Carbohydrate H-bond Asp47

- Carbohydrate H-bond Arg413

Region S5

Gly396 - conserved - Ala[*]

Ser397 - conserved - Thr

- essential for N-glycosylation

Met398 - not conserved - Leu, Trp[*]

Ser399 - not conserved - Asn, Ala

Glu400 - conserved

- not protected by acarbose

- lining cleft

- H-bond with Gln401

- H-bond with Tyr48, Ser411 ??

- stacked with Trp317 ??

Gln401 - conserved - Glu

- lining cleft

- H-bond with Glu400

- H-bond with Asn315 (structure stabilization ?)

Tyr402 - not conserved - Thr[*], Leu, Phe

- partial oxydation with N-bromosuccimidine when unprotected

Asp403 - not conserved - Asp, Gly[*], Asn

- not protected by acarbose EAC

Lys404 - not conserved - Arg, Asn[*

]- H-bond Leu291

Ser405 - not conserved - Tyr, Thr

Asp406 - not conserved - Thr

- non-reacting group EAC

Gly407 - conserved

Glu408 - not conserved - Tyr, Leu

- non-reacting group EAC

Gln409 - not conserved - Ser

Leu410 - not conserved - Thr

Ser411 - not conserved - Gly

- lining cleft

- H-bond with Glu400 ??

Ala412 - conserved

Arg413 - conserved - Tyr

- H-bond Carbohydrate Asn395

Asp414 - conserved - Ser

- non-reacting group EAC

- alpha-helix H13

Leu415 - conserved

- alpha-helix H13

Thr416 - conserved

- interaction with Asp55 on free side chain In active site ??

- alpha-helix H13

Trp417 - conserved

- protected by maltose, acarbose and isomaltose

?? - bottom of active site - block action

- stabilized by His254 ?

- alpha-helix H13

Ser418 - conserved

- alpha-helix H13

Tyr419 -not conserved - Ser, His

- partial oxydation with N-bromosuccimidine when unprotected

- alpha-helix H13

Ala420 - conserved - Gly

- alpha-helix H13

Ala421 - conserved - Ser

- alpha-helix H13

Leu422 - conserved

- alpha-helix H13

Leu423 - conserved - Ile

- alpha-helix H13

Thr424 - conserved - Glu

- alpha-helix H13

Ala425 - conserved

- alpha-helix H13

Region Pos-S5

Asn426 - not conserved - Ile, Ser

- alpha-helix H13

Asn427 - not conserved - Lys, Tyr

- alpha-helix H13

Arg428 - not conserved - Ala, Leu

- alpha-helix H13

Arg429 - conserved - Lys

- alpha-helix H13

Asn430 - conserved - Ala

- alpha-helix H13

Ser431 - not conserved - Lys, Gly

Val432 - conserved - Gly

Val433 - not conserved - Lys, Pro

Pro434 - conserved - Ala, Pro

Ala435 - conserved - Leu

Ser436 - not conserved - Ala

Trp437 - not matched

- protected by maltose, acarbose and isomaltose N-bromosuccinimide

Gly438 - not matched

Glu439 - not matched

- non-reacting or not protected by acarbose EAC

- alpha-helix N

- H-bond Thr266

Thr440 - not matched

- alpha-helix N

Ser441 - not matched

- O-glycosylation site

- alpha-helix N

Ala442 - not matched

- alpha-helix N

* Thr442 - thermosensitive

- O-glycosylated ??

Ser443 - not matched

- O-glycosylation site

- alpha-helix N

Ser444 - not matched

- O-glycosylation site

- alpha-helix N

Val445 - not matched

- alpha-helix N

Pro446 - not matched

Gly447 - not matched

Thr448 - not matched

Cys449 - not matched

- S-bond with Cys222

Ala450 - not matched

Ala451 - not matched

Thr452 - not matched

- O-glycosylation site

Ser453 - not matched

- O-glycosylation site

Ala454 - not matched

Ile455 - not matched

Gly456 - not matched

Thr457 - not matched

Tyr458 - not matched

- non-reacting group EAC

Ser459 - not matched

- O-glycosylation site

Ser460 - not matched

- O-glycosylation site

Val461 - not matched

Thr462 - not matched

- O-glycosylation site

Val463 - not matched

Thr464 - not matched

- O-glycosylation site

Ser465 - not matched

Trp466 - not matched

- not protected by acarbose N-bromosuccinimide

Pro467 - not matched

Ser468 - not matched

- O-glycosylation site

Ile469 - not matched

Val470 - not matched

Last Changed: 05/20/94


pedro@iastate.edu