DOI: 10.1126/science.1621098. An Unlikely Sugar Substrate Site in the 1.65 Å Structure of the Human Aldose Reductase Holoenzyme Implicated in Diabetic Complications

An Unlikely Sugar Substrate Site in the 1.65 Å Structure of the Human Aldose Reductase Holoenzyme Implicated in Diabetic Complications

10.1126/science.1621098

Crossref journal-article

American Association for the Advancement of Science (AAAS)

Science (221)

Abstract

Aldose reductase, which catalyzes the reduced form of nicotinamide adenine dinucleotide phosphate (NADPH)-dependent reduction of a wide variety of aromatic and aliphatic carbonyl compounds, is implicated in the development of diabetic and galactosemic complications involving the lens, retina, nerves, and kidney. A 1.65 angstrom refined structure of a recombinant human placenta aldose reductase reveals that the enzyme contains a parallel β8/α8-barrel motif and establishes a new motif for NADP-binding oxidoreductases. The substrate-binding site is located in a large, deep elliptical pocket at the COOH-terminal end of the β barrel with a bound NADPH in an extended conformation. The highly hydrophobic nature of the active site pocket greatly favors aromatic and apolar substrates over highly polar monosaccharides. The structure should allow for the rational design of specific inhibitors that might provide molecular understanding of the catalytic mechanism, as well as possible therapeutic agents.

Bibliography

Wilson, D. K., Bohren, K. M., Gabbay, K. H., & Quiocho, F. A. (1992). An Unlikely Sugar Substrate Site in the 1.65 Ã Structure of the Human Aldose Reductase Holoenzyme Implicated in Diabetic Complications. Science, 257(5066), 81â84.

Authors 4

David K. Wilson (first)
Kurt M. Bohren (additional)
Kenneth H. Gabbay (additional)
Florante A. Quiocho (additional)

References 40 Referenced 344

10.1126/science.230.4722.144
BHATNAGAR, A, INHIBITION-KINETICS OF HUMAN KIDNEY ALDOSE AND ALDEHYDE REDUCTASES BY ALDOSE REDUCTASE INHIBITORS, BIOCHEMICAL PHARMACOLOGY 39: 1115 (1990). (10.1016/0006-2952(90)90292-S) / BIOCHEMICAL PHARMACOLOGY (1990)
BOHREN, K.M., THE ALDO-KETO REDUCTASE SUPERFAMILY - CDNAS AND DEDUCED AMINO-ACID SEQUENCES OF HUMAN ALDEHYDE AND ALDOSE REDUCTASES, JOURNAL OF BIOLOGICAL CHEMISTRY 264: 9547 (1989). (10.1016/S0021-9258(18)60566-6) / JOURNAL OF BIOLOGICAL CHEMISTRY (1989)
BOHREN, K.M., EXPRESSION OF HUMAN ALDOSE AND ALDEHYDE REDUCTASES - SITE-DIRECTED MUTAGENESIS OF A CRITICAL LYSINE-262, JOURNAL OF BIOLOGICAL CHEMISTRY 266: 24031 (1991). (10.1016/S0021-9258(18)54387-8) / JOURNAL OF BIOLOGICAL CHEMISTRY (1991)
BOLIN, J.T., CRYSTAL-STRUCTURES OF ESCHERICHIA-COLI AND LACTOBACILLUS-CASEI DIHYDROFOLATE-REDUCTASE REFINED AT 1.7 A RESOLUTION .1. GENERAL FEATURES AND BINDING OF METHOTREXATE, JOURNAL OF BIOLOGICAL CHEMISTRY 257: 3650 (1982). (10.1016/S0021-9258(18)34829-4) / JOURNAL OF BIOLOGICAL CHEMISTRY (1982)
BOULTON, AJM, A MULTICENTER TRIAL OF THE ALDOSE-REDUCTASE INHIBITOR, TOLRESTAT, IN PATIENTS WITH SYMPTOMATIC DIABETIC NEUROPATHY, DIABETOLOGIA 33: 431 (1990). (10.1007/BF00404095) / DIABETOLOGIA (1990)
BRANDEN, C.I., CURR OPIN STRUC BIOL 1: 978 (1991). (10.1016/0959-440X(91)90094-A) / CURR OPIN STRUC BIOL (1991)
Brunger A. T. XPLOR A System for Crystallography and NMR 2.1 Manual (1990).
CARSON, M, RIBBON MODELS OF MACROMOLECULES, JOURNAL OF MOLECULAR GRAPHICS 5: 103 (1987). (10.1016/0263-7855(87)80010-3) / JOURNAL OF MOLECULAR GRAPHICS (1987)
10.1126/science.182.4117.1146
Einspahr H. M. Transaction of the American Crystallographic Association 25 (1989).
FARBER, G.K., THE EVOLUTION OF ALPHA-BETA-BARREL ENZYMES, TRENDS IN BIOCHEMICAL SCIENCES 15: 228 (1990). (10.1016/0968-0004(90)90035-A) / TRENDS IN BIOCHEMICAL SCIENCES (1990)
Feldman, H. B., Biochimica et Biophysica Acta (BBA)-Enzymology 480: 14 (1977). (10.1016/0005-2744(77)90316-3) / Biochimica et Biophysica Acta (BBA)-Enzymology (1977)
GABBAY, K.H., SORBITOL PATHWAY AND COMPLICATIONS OF DIABETES, NEW ENGLAND JOURNAL OF MEDICINE 288: 831 (1973). (10.1056/NEJM197304192881609) / NEW ENGLAND JOURNAL OF MEDICINE (1973)
10.1021/bi00439a006
GRIMSHAW, C.E., MECHANISTIC BASIS FOR NONLINEAR KINETICS OF ALDEHYDE REDUCTION CATALYZED BY ALDOSE REDUCTASE, BIOCHEMISTRY 29: 9947 (1990). (10.1021/bi00494a027) / BIOCHEMISTRY (1990)
10.1126/science.2402636
KADOR, P.F., THE PHARMACOLOGY OF ALDOSE REDUCTASE INHIBITORS, ANNUAL REVIEW OF PHARMACOLOGY AND TOXICOLOGY 25: 691 (1985). (10.1146/annurev.pa.25.040185.003355) / ANNUAL REVIEW OF PHARMACOLOGY AND TOXICOLOGY (1985)
KADOR, P.F., THE ROLE OF ALDOSE REDUCTASE IN THE DEVELOPMENT OF DIABETIC COMPLICATIONS, MEDICINAL RESEARCH REVIEWS 8: 325 (1988). (10.1002/med.2610080302) / MEDICINAL RESEARCH REVIEWS (1988)
KURIYAN, J, CONVERGENT EVOLUTION OF SIMILAR FUNCTION IN 2 STRUCTURALLY DIVERGENT ENZYMES, NATURE 352: 172 (1991). (10.1038/352172a0) / NATURE (1991)
LEE, B, INTERPRETATION OF PROTEIN STRUCTURES - ESTIMATION OF STATIC ACCESSIBILITY, JOURNAL OF MOLECULAR BIOLOGY 55: 379 (1971). (10.1016/0022-2836(71)90324-X) / JOURNAL OF MOLECULAR BIOLOGY (1971)
LUECKE, H, HIGH SPECIFICITY OF A PHOSPHATE-TRANSPORT PROTEIN DETERMINED BY HYDROGEN-BONDS, NATURE 347: 402 (1990). (10.1038/347402a0) / NATURE (1990)
MARTYN, C.N., 6-MONTH TREATMENT WITH SORBINIL IN ASYMPTOMATIC DIABETIC NEUROPATHY - FAILURE TO IMPROVE ABNORMAL NERVE FUNCTION, DIABETES 36: 987 (1987). (10.2337/diab.36.9.987) / DIABETES (1987)
OBRIEN, M.M., INHIBITION OF HUMAN-BRAIN ALDOSE REDUCTASE AND HEXONATE DEHYDROGENASE BY ALRESTATIN AND SORBINIL, JOURNAL OF NEUROCHEMISTRY 39: 810 (1982). (10.1111/j.1471-4159.1982.tb07964.x) / JOURNAL OF NEUROCHEMISTRY (1982)
PAI, E.F., CURRENT OPINION STRU 1: 796 (1991). (10.1016/0959-440X(91)90181-R) / CURRENT OPINION STRU (1991)
POULSOM, R, INHIBITION OF HEXONATE DEHYDROGENASE AND ALDOSE REDUCTASE FROM BOVINE RETINA BY SORBINIL, STATIL, M79175 AND VALPROATE, BIOCHEMICAL PHARMACOLOGY 35: 2955 (1986). (10.1016/0006-2952(86)90492-2) / BIOCHEMICAL PHARMACOLOGY (1986)
PRIESTLE, J.P., RIBBON - A STEREO CARTOON DRAWING PROGRAM FOR PROTEINS, JOURNAL OF APPLIED CRYSTALLOGRAPHY 21: 572 (1988). (10.1107/S0021889888005746) / JOURNAL OF APPLIED CRYSTALLOGRAPHY (1988)
QUIOCHO, F.A., CARBOHYDRATE-BINDING PROTEINS - TERTIARY STRUCTURES AND PROTEIN-SUGAR INTERACTIONS, ANNUAL REVIEW OF BIOCHEMISTRY 55: 287 (1986). (10.1146/annurev.bi.55.070186.001443) / ANNUAL REVIEW OF BIOCHEMISTRY (1986)
QUIOCHO, F.A., STABILIZATION OF CHARGES ON ISOLATED IONIC GROUPS SEQUESTERED IN PROTEINS BY POLARIZED PEPTIDE UNITS, NATURE 329: 561 (1987). (10.1038/329561a0) / NATURE (1987)
QUIOCHO, F.A., PROTEIN-CARBOHYDRATE INTERACTIONS - BASIC MOLECULAR-FEATURES, PURE AND APPLIED CHEMISTRY 61: 1293 (1989). (10.1351/pac198961071293) / PURE AND APPLIED CHEMISTRY (1989)
Rose, I. A., Proceedings of the National Academy of Sciences of the United States of America 77: 2439 (1980). / Proceedings of the National Academy of Sciences of the United States of America (1980)
SACK, J.S., JOURNAL OF MOLECULAR GRAPHICS 6: 224 (1988). / JOURNAL OF MOLECULAR GRAPHICS (1988)
SPIELBERG, S.P., INVITRO ASSESSMENT OF A HYPERSENSITIVITY SYNDROME ASSOCIATED WITH SORBINIL, ANNALS OF INTERNAL MEDICINE 114: 720 (1991). (10.7326/0003-4819-114-9-720) / ANNALS OF INTERNAL MEDICINE (1991)
TOMAREV, S.I., A NOVEL TYPE OF CRYSTALLIN IN THE FROG EYE LENS - 35-KDA POLYPEPTIDE IS NOT HOMOLOGOUS TO ANY OF THE MAJOR CLASSES OF LENS CRYSTALLINS, FEBS LETTERS 171: 297 (1984). (10.1016/0014-5793(84)80508-6) / FEBS LETTERS (1984)
VYAS, N.K., CURR OPIN STRUC BIOL 1: 732 (1991). (10.1016/0959-440X(91)90172-P) / CURR OPIN STRUC BIOL (1991)
WATANABE, K, STRUCTURAL SIMILARITY OF BOVINE LUNG PROSTAGLANDIN-F SYNTHASE TO LENS EPSILON-CRYSTALLIN OF THE EUROPEAN COMMON FROG, PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA 85: 11 (1988). / PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA (1988)
Wermuth, B., Enzymology of Carbonyl Metabolism: Aldehyde Dehydrogenase, Aldo/Keto Reductase and Alcohol Dehydrogenase: 261 (1992). / Enzymology of Carbonyl Metabolism: Aldehyde Dehydrogenase, Aldo/Keto Reductase and Alcohol Dehydrogenase (1992)
WERMUTH, B, PURIFICATION AND CHARACTERIZATION OF HUMAN-BRAIN ALDOSE REDUCTASE, EUROPEAN JOURNAL OF BIOCHEMISTRY 127: 279 (1982). (10.1111/j.1432-1033.1982.tb06867.x) / EUROPEAN JOURNAL OF BIOCHEMISTRY (1982)
10.1126/science.1925539
WINTERS, C.J., ISOLATION AND CHARACTERIZATION OF CLONED CDNAS ENCODING HUMAN-LIVER CHLORDECONE REDUCTASE, BIOCHEMISTRY 29: 1080 (1990). (10.1021/bi00456a034) / BIOCHEMISTRY (1990)

Dates

Type	When
Created	18 years, 10 months ago (Oct. 5, 2006, 7:03 p.m.)
Deposited	1 year, 7 months ago (Jan. 11, 2024, 4:01 a.m.)
Indexed	4 months, 1 week ago (April 18, 2025, 5:23 a.m.)
Issued	33 years, 1 month ago (July 3, 1992)
Published	33 years, 1 month ago (July 3, 1992)
Published Print	33 years, 1 month ago (July 3, 1992)

Funders 0

None

BibTeX

@article{Wilson_1992, title={An Unlikely Sugar Substrate Site in the 1.65 Å Structure of the Human Aldose Reductase Holoenzyme Implicated in Diabetic Complications}, volume={257}, ISSN={1095-9203}, url={http://dx.doi.org/10.1126/science.1621098}, DOI={10.1126/science.1621098}, number={5066}, journal={Science}, publisher={American Association for the Advancement of Science (AAAS)}, author={Wilson, David K. and Bohren, Kurt M. and Gabbay, Kenneth H. and Quiocho, Florante A.}, year={1992}, month=jul, pages={81–84} }

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