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| - | [[Image:2bgq.png|left|200px|thumb|Crystal structure of Aldose Reductase [[2bgq]]]]
| + | <StructureSection load='1ads' size='400' side='right' caption='Human aldose reductase complex with cofactor NADP (PDB code [[1ads]])' scene='43/436098/Cv/2'> |
| - | {{STRUCTURE_2bgq| PDB=2bgq | SIZE=400| SCENE=Aldose_Reductase/Cv/1 |right|CAPTION=Barley aldose reductase complex with sulfate [[2bgq]] }}
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| - | [[Aldose Reductase]] (AldR) is an NADPH-dependent enzyme which reduces aldehydes and carbonyls. It reduces glucose to sorbitol in the glucose metabolism pathway. The AldR is implicated in diabetics and causing Iodine Deficiency Disorder (IDD) and its treatment involves the use of IDD inhibitors of AldR. The images at the left and at the right correspond to one representative AldR, ''i.e.'' the crystal structure of barley apo-Aldose Reductase ([[2bgq]]).
| + | == Function == |
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| - | '''Fructose bisphosphate aldolase''' is an enzyme in glycolysis and gluconeogenesis. Glycolyis is responsible for the conversion of glucose into two three-carbon pyruvate molecules without the need for oxygen. The process generates two net ATP. The overall reaction is:
| + | [[Aldose Reductase]] (AldR) is an NADPH-dependent enzyme which reduces aldehydes and carbonyls. It reduces glucose to sorbitol in the glucose metabolism pathway.<ref>PMID:1734286</ref> |
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| - | Glucose + 2 NAD+ + 2 ADP + 2 Pi --> 2 pyruvate (3-carbon product) + 2 NADH + 2 ATP + 2 H20 + 4 H+
| + | == Disease == |
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| - | Gluconeogenesis is responsible for maintaining the appropriate levels of blood glucose in animals by generating glucose from non-carbohydrate precursors. Gluconeogenesis can make glucose from lactate, pyruvate, citric acid cycle intermediates and from most amino acids (the exceptions being leucine and lysine). The common intermediate for all of the precursors on their way to becoming glucose must be oxaloacetate.
| + | The AldR is implicated in diabetics and causing Iodine Deficiency Disorder (IDD) and its treatment involves the use of IDD inhibitors of AldR. |
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| - | The aldolase catalyzes the reversible cleavage of fructose-1,6-bisphosphate into dihydroxyacetone phosphate (DHAP) and glyceraldehyde-3-phosphate (GAP). Different isozymes of aldolase can also catalyze the cleavage of fructose 1-phosphate to diydroxyacetone and glyceraldehyde (GA). Different isozymes exhibit preferences for either or both of the substrates, depending on the role of the aldolase (i.e. gluconeogenesis versus glycolysis).<ref name="book">Voet, D, Voet, J, & Pratt, C. (2008). Fundamentals of biochemistry, third edition. Hoboken, NJ: Wiley & Sons, Inc.</ref>
| + | == Structural highlights == |
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| - | <br /> | + | AldR structure is of a <scene name='43/436098/Cv/3'>β/α-barrel</scene>. The <scene name='43/436098/Cv/8'>active site is located in the barrel core</scene>.<ref>PMID:1621098</ref> |
| - | <br /> | + | *<scene name='43/436098/Cv/7'>Active site interactions</scene>. Water molecules are shown as red spheres. |
| - | <br /> | + | *<scene name='43/436098/Cv/9'>Active site tunnel</scene>. |
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| - | == 3D Structures of Aldose Reductase == | + | == 3D Structures of aldose reductase == |
| | + | [[Aldose reductase 3D structures]] |
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| - | ''Update January 2013''
| + | </StructureSection> |
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| - | ===Aldose Reductase=== | + | == References == |
| - | | + | <references/> |
| - | [[1abn]], [[1ads]], [[3q65]] - hAldR +NADP – human<br />
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| - | [[1xgd]] – hAldR (mutant)<br />
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| - | [[3q67]] – hAldR (mutant)+NADP<br />
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| - | [[3afm]] – SsAldR A1-R – ''Sphingomonas sp.''<br />
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| - | [[3afn]] - SsAldR A1-R+NADP<br />
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| - | [[1dla]] – pAldR - pig<br />
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| - | [[1ah4]] - pAldR+NADP<br />
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| - | [[3krb]] – AldR+NADP – ''Ghiardia lamblia''<br />
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| - | [[2bgq]] – bAldR - barley<br />
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| - | [[2bgs]] - bAldR+NADP<br />
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| - | ===Aldose Reductase+inhibitors===
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| - | [[3ghr]], [[3ghs]], [[3ght]], [[3ghu]], [[2r24]], [[2pzn]], [[3g5e]], [[2qxw]], [[2iki]], [[2i16]], [[2i17]], [[1t40]], [[1t41]], [[1us0]], [[1el3]], [[3t42]] - hAldR +NADP+IDD inhibitors<br />
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| - | [[3onb]], [[3onc]] – hAldR (mutant) +NADP+IDD inhibitor<br />
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| - | [[3u2c]] - hAldR +NADP+ NSAID inhibitor<br />
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| - | [[3bcj]], [[1x97]], [[1x98]], [[1pwm]], [[1ef3]] - hAldR+NADP+fidarestat<br />
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| - | [[2pd5]], [[2dux]], [[2duz]], [[2dv0]], [[2fz8]], [[2fz9]], [[2hv5]], [[2hvn]], [[2hvo]], [[1mar]] - hAldR+NADP+zopolrestat<br />
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| - | [[2fzb]], [[2fzd]] - hAldR+NADP+tolrestat<br />
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| - | [[1z3n]] - hAldR+NADP+lidorestat<br />
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| - | [[1pwl]] - hAldR+NADP+minalrestat<br />
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| - | [[1iei]] - hAldR+NADP+zenarestat<br />
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| - | [[1z89]], [[1z8a]] - hAldR+NADP+sulfonyl-pyridazinone<br />
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| - | [[2pdg]], [[2pdh]] - hAldR+NADP+uracil inhibitor<br />
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| - | [[2j8t]], [[1x96]], [[2acs]], [[2acu]] - hAldR+NADP+citrate<br />
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| - | [[2acq]] - hAldR +NADP+glucose phosphate<br />
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| - | [[2acr]] - hAldR +NADP+cacodylate<br />
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| - | [[2ikg]], [[2ikh]], [[2ikj]], [[3v35]] - hAldR+NADP+nitro-substituted inhibitor<br />
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| - | [[3v36]] - hAldR+NADP+ glyceraldehyde + azine<br />
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| - | [[2nvc]], [[2nvd]] - hAldR+NADP+isothiazole inhibitor<br />
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| - | [[3p2v]] - hAldR+NADP+ benzothiazepine inhibitor<br />
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| - | [[2pev]], [[2pf8]], [[2pfh]] - hAldR+NADP+IDD inhibitor+ fidarestat<br />
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| - | [[2ipw]], [[2iq0]], [[2iqd]], [[2isf]], [[2ine]], [[2inz]], [[2is7]] - hAldR+NADP+ acid<br />
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| - | [[2f2k]] - hAldR+NADP+DEG<br />
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| - | [[2pdn]], [[2pdq]] – hAldR (mutant)+NADP+uracil inhibitor<br />
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| - | [[2pdb]], [[2pdf]], [[2pdi]], [[2pdm]], [[2pdx]], [[3len]], [[3m0i]], [[3mb9]] – hAldR (mutant)+NADP+zopolrestat<br />
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| - | [[2pd9]], [[2pdw]], [[2pdy]], [[2agt]] – hAldR (mutant)+NADP+fidarestat<br />
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| - | [[2pdk]] - hAldR (mutant)+NADP+sorbinil<br />
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| - | [[2pdl]] - hAldR (mutant)+NADP+tolrestat<br />
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| - | [[1az1]] – hAldR (mutant)+NADP+alrestatin<br />
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| - | [[1az2]] - hAldR (mutant)+NADP+citrate<br />
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| - | [[3lbo]], [[3ld5]], [[3lql]], [[3lz5]], [[2pdc]], [[3lep]], [[3lqg]], [[3lz3]], [[3m4h]], [[2pdj]], [[2pdp]], [[2pdu]], [[3m64]], [[3mc5]] - hAldR (mutant)+IDD inhibitors<br />
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| - | [[3dn5]] – hAldR+NADP+biaryl inhibitor<br />
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| - | [[3rx2]], [[3rx3]], [[3rx4]], [[3s3g]] - hAldR+NADP+ sulindac inhibitor<br />
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| - | [[3fx4]] – pAldR+NADP+thiazolidine derivative <br />
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| - | [[3h4g]] – pAldR+NADP+fidarestat<br />
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| - | [[1ah3]] - pAldR+NADP+tolrestat<br />
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| - | [[1ah0]] - pAldR+NADP+sorbinil<br />
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| - | [[1eko]] - pAldR+NADP+IDD inhibitor<br />
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| - | [[2vdg]] – bAldR+NADP+butanol <br />
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