2

Supplemental Table 1 Domains and conserved regions or amino acids of AtHXKs with respect to ScHXK2

YHK2 HXK1 HXK2 HXK3 HKL1 HKL2 HKL3

Large domain 13-76 27-91 27-91 32-94 27-91 27-91 28-92

212-457 230-475 230-475 235-476 230-483 231-479 231-470

Small domain 77-211 92-229 92-229 95-234 92-229 92-230 93-230

458-486 476-496 476-502 477-493 484-498 480-502 471-493

Phosphate 1 82-103 97-118 cons cons not cons not cons not cons

Loop 1 87-91 102-106 cons cons uncer uncer not cons

Loop 2 115-124 not cons not cons not cons not cons not cons not cons

Sugar binding core 148-167 167-186 cons cons uncer uncer not cons

Loop 3 158-163 177-182 cons cons cons cons not cons

Loop 4 174-178 193-197 cons cons cons cons not cons

Connect 1 203-223 222-242 cons cons not cons not cons not cons

Phosphate 2 229-248 248-267 cons cons cons cons not cons

Thr234 Thr253 cons cons cons cons Met

Adenosine 411-439 425-461 cons cons insert insert not cons

Ser419 Gly441 Gly Ala Gly Gly Gly

Connect 2 453-473 471-491 cons cons cons cons cons

Hydrophobic Ile85 Leu100 Leu100 Leu103 Leu100 Leu100 Val101

Channel Leu87 Leu102 Leu102 Leu105 Leu102 Leu102 Leu103

Leu127 Leu143 Leu143 Leu146 Leu143 Leu143 Leu144

Ile131 Ile147 Ile147 Ile150 Leu147 Leu147 Ile148

Leu135 Leu151 Leu151 Leu154 Leu151 Leu151 Leu152

Ile139 Val155 Val155 Val158 Ile155 Ile155 Leu156

Leu153 Leu172 Leu172 Leu176 Leu171 Leu172 Leu170

Phe155 Phe174 Phe174 Phe178 Phe173 Phe174 Phe172

Phe157 Phe176 Phe176 Phe180 Phe175 Phe176 Phe174

Phe178 Phe197 Phe197 Phe201 Phe196 Phe197 Asn186

Leu192 Leu211 Leu211 Leu215 Leu210 Leu211 Met200

Ile196 Leu215 Met215 Met219 Leu214 Leu215 Leu204

Catalytic residues Lys176 Lys195 cons cons cons cons Leu

Asp211 Asp230 cons cons cons cons Asn

Supplemental Table 1 Continued

YHK2 HXK1 HXK2 HXK3 HKL1 HKL2 HKL3

Glucose contacts Ser158 Ser177 cons cons cons cons Thr

Asn237 Asn256 cons cons cons cons cons

Glu269 Glu284 cons cons cons cons cons Glu302 Glu315 cons cons cons cons cons

Conserved Gly Gly76 Gly91 Gly91 Gly94 Gly91 Gly91 Gly92

Gly80 Gly95 Gly95 Gly98 Gly95 Gly95 Gly96

Gly88 Gly103 Gly103 Gly106 Gly103 Gly103 Arg104

Gly154 Gly173 Gly173 Gly177 Ala172 Ala173 Gly171

Gly233 Gly252 Gly252 Gly256 Gly251 Gly252 Gly252

Gly235 Gly254 Gly254 Gly258 Gly253 Gly254 Gly254

Gly297 Gly310 Gly310 Gly312 Asn309 Asn310 Gly310

Gly307 Gly320 Gly320 Gly322 Gly319 Gly320 Gly320

Gly418 Gly440 Gly440 Gly441 Gly447 Gly444 Gly435

Gly461 Gly479 Gly479 Gly480 Ser486 Ser483 Ala474

Amino acid sequences were aligned using ClustalW in BioEdit. Annotations are based on regions homologous to yeast hexokinase II (Kuser et al. 2000). Designation of structural motifs as conserved (= cons), not conserved, or uncertain (uncer) is based on visual inspection and a relative assessment of the number of amino acid changes. However, the functional significance for a given motif change is not generally known such that the score of some motifs has some inherent ambiguity. For example, Loop 1 is LGGTN. This is changed in HKL1 to LGGTY and scored as uncertain with regard to whether this modified loop would still have similar functional capability. However, Loop 1 is more extensively changed in HKL3 to LRGKE and is scored as not conserved. Loop 2 in YHK2 is PDAMRTTQNP. The corresponding region in AtHXK1 is SIPPHLMTGG, but the function might still be retained even though the sequence is completely different. Loop 3 in YHK2 is SFPPASQ, which is present in most of the HXKs as SFPVKQ. This similarity was scored as conserved, except for the much more divergent sequence in HKL3 (TRSVEQ). The core sugar binding motif in YHK2 is LGFTFSF---Q--I, but in AtHXKs the conserved motif is LGFTFSF--Q--L/I. Both HKL1 and HKL2 were scored as having uncertain conservation of the core sugar sequence motif. HKL1 has a sequence of LAFTFSF------I, while HKL2 has a less divergent sequence of LAFTFSF---Q--I. YHK2 = yeast hexokinase 2; HXK1 = At4g29130; HXK2 = At2g19860; HXK3 = At1g47840; HKL1 = At1g50460; HKL2 = At3g20040; HKL3 = At4g37840.