Structure of PDB 4k26 Chain B

Receptor sequence

>4k26B (length=265) Species: 10090 (Mus musculus)

EEFRPEMLQGKKVIVTGASKGIGREMAYHLSKMGAHVVLTARSEEGLQKV
VSRCLELGAASAHYIAGTMEDMTFAEQFIVKAGKLMGGLDMLILNHITQT
SLSLFHDDIHSVRRVMEVNFLSYVVMSTAALPMLKQSNGSIAVISSLAGK
MTQPMIAPYSASKFALDGFFSTIRTELYITKVNVSITLCVLGLIDTETAM
KEISGIINAQASPKEECALEIIKGTALRKSEVYYDKSPLTPILLGNPGRK
IMEFFSLRYYNKDMF

3D structure

• PDB: 4k26 1,1-Dioxo-5,6-dihydro-[4,1,2]oxathiazines, a novel class of 11-HSD1 inhibitors for the treatment of diabetes.
• Chain: B
• Resolution: 2.21 Å

Enzymatic activity

• Catalytic site (original residue number in PDB): S170 Y183 K187
• Catalytic site (residue number reindexed from 1): S146 Y159 K163
• Enzyme Commision number: 1.1.1.146: 11beta-hydroxysteroid dehydrogenase.
  1.1.1.201: 7beta-hydroxysteroid dehydrogenase (NADP(+)).

Interaction with ligand

Site #	Ligand	Ligand chain	Binding residues on receptor (original residue number in PDB)	Binding residues on receptor (residue number reindexed from 1)	Binding affinity
BS01	SFF	B	I121 S170 L171 A172 Q177 Y183 I227 I231	I97 S146 L147 A148 Q153 Y159 I203 I207	MOAD: ic50=1.22uM
BS02	NDP	B	G41 S43 K44 G45 I46 R66 S67 T92 M93 N119 I121 I168 S170 Y183 K187 L215 G216 L217 I218 T220 T222 A223	G17 S19 K20 G21 I22 R42 S43 T68 M69 N95 I97 I144 S146 Y159 K163 L191 G192 L193 I194 T196 T198 A199

Gene Ontology

Molecular Function

• GO:0016491 oxidoreductase activity
• GO:0042803 protein homodimerization activity
• GO:0047022 7-beta-hydroxysteroid dehydrogenase (NADP+) activity
• GO:0050661 NADP binding
• GO:0070524 11-beta-hydroxysteroid dehydrogenase (NADP+) activity

Biological Process

• GO:0008202 steroid metabolic process
• GO:0030324 lung development

Cellular Component

• GO:0005783 endoplasmic reticulum
• GO:0005789 endoplasmic reticulum membrane
• GO:0016020 membrane

External links

• PDB: RCSB:4k26, PDBe:4k26, PDBj:4k26
• PDBsum: 4k26
• PubMed: 23845218
• UniProt: P50172|DHI1_MOUSE 11-beta-hydroxysteroid dehydrogenase 1 (Gene Name=Hsd11b1)