Aldose Reductase

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(New page: Crystal structure of Aldose Reductase 2bgq {{STRUCTURE_2bgq| PDB=2bgq | SIZE=300| SCENE= |right|CAPTION=Aldose Reductase 2bgq }} [[Aldose Red...)
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[[Image:2bgq.png|left|200px|thumb|Crystal structure of Aldose Reductase [[2bgq]]]]
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<StructureSection load='1ads' size='400' side='right' caption='Human aldose reductase complex with cofactor NADP (PDB code [[1ads]])' scene='43/436098/Cv/2'>
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{{STRUCTURE_2bgq| PDB=2bgq | SIZE=300| SCENE= |right|CAPTION=Aldose Reductase [[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]]).
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== Function ==
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{{TOC limit|limit=2}}
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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.<ref>PMID:1734286</ref>
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== 3D Structures of Aldose Reductase ==
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== Disease ==
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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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===Aldose Reductase===
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== Structural highlights ==
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[[1abn]], [[1ads]] - hAldR +NADP – human
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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>
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[[1xgd]] – hAldR (mutant)
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*<scene name='43/436098/Cv/7'>Active site interactions</scene>. Water molecules are shown as red spheres.
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[[3q67]] – hAldR (mutant)+NADP
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*<scene name='43/436098/Cv/9'>Active site tunnel</scene>.
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[[3afm]] – SsAldR A1-R – Sphingomonas sp.
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[[3afn]] - SsAldR A1-R+NADP
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[[1dla]] – pAldR - pig
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[[1ah4]] - pAldR+NADP
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[[3krb]] – AldR+NADP – Ghiardia lamblia
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[[2bgq]] – bAldR - barley
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[[2bgs]] - bAldR+NADP
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===Aldose Reductase+inhibitors===
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== 3D Structures of aldose reductase ==
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[[Aldose reductase 3D structures]]
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3ghr, 3ghs, 3ght, 3ghu, 2r24, 2pzn, 3g5e, 2qxw, 2iki, 2i16, 2i17, 1t40, 1t41, 1us0, iel3 - hAldR +NADP+IDD inhibitors
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</StructureSection>
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3bcj, 1x97, 1x98, 1pwm, 1ef3 - hAldR+NADP+fidarestat
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2pd5, 2dux, 2duz, 2dv0, 2fz8, 2fz9, 2hv5, 2hvn, 2hvo, 1mar - hAldR+NADP+zopolrestat
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== References ==
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2fzb, 2fzd - hAldR+NADP+tolrestat
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<references/>
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1z3n - hAldR+NADP+lidorestat
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1pwl - hAldR+NADP+minalrestat
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1iei - hAldR+NADP+zenarestat
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1z89, 1z8a - hAldR+NADP+sulfonyl-pyridazinone
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2pdg, 2pdh - hAldR+NADP+uracil inhibitor
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2j8t, 1x96, 2acs, 2acu - hAldR+NADP+citrate
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2acq - hAldR +NADP+glucose phosphate
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2acr - hAldR +NADP+cacodylate
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2ikg, 2ikh, 2ikj - hAldR+NADP+nitro-substituted inhibitor
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2nvc, 2nvd - hAldR+NADP+isothiazole inhibitor
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2pev, 2pf8, 2pfh - hAldR+NADP+IDD inhibitor+ fidarestat
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2ipw, 2iq0, 2iqd, 2isf, 2ine, 2inz, 2is7 - hAldR+NADP+ acid
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2f2k - hAldR+NADP+DEG
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2pdn, 2pdq – hAldR (mutant)+NADP+uracil inhibitor
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2pdb, 2pdf, 2pdi, 2pdm, 2pdx – hAldR (mutant)+NADP+zopolrestat
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2pd9, 2pdw, 2pdy, 2agt – hAldR (mutant)+NADP+fidarestat
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2pdk - hAldR (mutant)+NADP+sorbinil
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2pdl - hAldR (mutant)+NADP+tolrestat
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1az1 – hAldR (mutant)+NADP+alrestatin
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1az2 - hAldR (mutant)+NADP+citrate
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3lbo, 3ld5, 3lq, 3lz5l, 2pdc, 3lep, 3lqg, 3lz3, 3m4h, 2pdj, 2pdp, 2pdu - hAldR (mutant)+IDD inhibitors
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3dn5 – hAldR+NADP+biaryl inhibitor
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3fx4 – pAldR+NAP+thiazolidine derivative
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3h4g – pAldR+NADP+fidarestat
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1ah3 - pAldR+NADP+tolrestat
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1ah0 - pAldR+NADP+sorbinil
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1eko - pAldR+NADP+IDD inhibitor
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2vdg – bAldR+NADP+butanol
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[[Category:Topic Page]]
[[Category:Topic Page]]

Current revision

Human aldose reductase complex with cofactor NADP (PDB code 1ads)

Drag the structure with the mouse to rotate

References

  1. ↑ Rondeau JM, Tete-Favier F, Podjarny A, Reymann JM, Barth P, Biellmann JF, Moras D. Novel NADPH-binding domain revealed by the crystal structure of aldose reductase. Nature. 1992 Jan 30;355(6359):469-72. PMID:1734286 doi:http://dx.doi.org/10.1038/355469a0
  2. ↑ Wilson DK, Bohren KM, Gabbay KH, Quiocho FA. An unlikely sugar substrate site in the 1.65 A structure of the human aldose reductase holoenzyme implicated in diabetic complications. Science. 1992 Jul 3;257(5066):81-4. PMID:1621098

Proteopedia Page Contributors and Editors (what is this?)

Michal Harel, Alexander Berchansky

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