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From Proteopedia

1evy, resolution 1.75Å ()
Ligands:
Activity:	Glycerol-3-phosphate dehydrogenase (NAD(+)), with EC number 1.1.1.8
Domains:	NAD_Gly3P_dh_C, gpsA, NAD_Gly3P_dh_N
Related:	1evz
Structural annotation: Resources: CATH : 1Evya01, 1Evya02 InterPro : Ipr011128, Ipr013328, Ipr006109, Ipr006168, Ipr008927 Pfam : PF07479, PF01210 SCOP : d1evya1, d1evya2 UniProt : P90551
Functional annotation: Cellular component: cytoplasm glycosome glycerol-3-phosphate dehydrogenase complex Biological process: glycerol-3-phosphate catabolic process glycerol-3-phosphate metabolic process carbohydrate metabolic process Molecular function: glycerol-3-phosphate dehydrogenase (NAD+) activity oxidoreductase activity, acting on CH-OH group of donors coenzyme binding NAD binding oxidoreductase activity oxidoreductase activity, acting on the CH-OH group of donors, NAD or NADP as acceptor
Evolutionary conservation: Toggle Conservation Colors: Rows = identical sequences: Further Information: Caveats, Explanation, Complete Results at ConSurfDB
Resources:	FirstGlance, OCA, PDBsum, RCSB
Coordinates:	save as pdb, mmCIF, xml

CRYSTAL STRUCTURE OF LEISHMANIA MEXICANA GLYCEROL-3-PHOSPHATE DEHYDROGENASE

Publication Abstract from PubMed

BACKGROUND: NAD-dependent glycerol-3-phosphate dehydrogenase (GPDH) catalyzes the interconversion of dihydroxyacetone phosphate and L-glycerol-3-phosphate. Although the enzyme has been characterized and cloned from a number of sources, until now no three-dimensional structure has been determined for this enzyme. Although the utility of this enzyme as a drug target against Leishmania mexicana is yet to be established, the critical role played by GPDH in the long slender bloodstream form of the related kinetoplastid Trypanosoma brucei makes it a viable drug target against sleeping sickness.

RESULTS: The 1.75 A crystal structure of apo GPDH from L. mexicana was determined by multiwavelength anomalous diffraction (MAD) techniques, and used to solve the 2.8 A holo structure in complex with NADH. Each 39 kDa subunit of the dimeric enzyme contains a 189-residue N-terminal NAD-binding domain and a 156-residue C-terminal substrate-binding domain. Significant parts of both domains share structural similarity with plant acetohydroxyacid isomeroreductase. The discovery of extra, fatty-acid like, density buried inside the C-terminal domain indicates a possible post-translational modification with an associated biological function.

CONCLUSIONS: The crystal structure of GPDH from L. mexicana is the first structure of this enzyme from any source and, in view of the sequence identity of 63%, serves as a valid model for the T. brucei enzyme. The differences between the human and trypanosomal enzymes are extensive, with only 29% sequence identity between the parasite and host enzyme, and support the feasibility of exploiting the NADH-binding site to develop selective inhibitors against trypanosomal GPDH. The structure also offers a plausible explanation for the observed inhibition of the T. brucei enzyme by melarsen oxide, the active form of the trypanocidal drugs melarsoprol and cymelarsan.

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

About this Structure

1EVY is a 1 chain structure of sequence from Leishmania mexicana. Full crystallographic information is available from OCA.

Reference

• Suresh S, Turley S, Opperdoes FR, Michels PA, Hol WG. A potential target enzyme for trypanocidal drugs revealed by the crystal structure of NAD-dependent glycerol-3-phosphate dehydrogenase from Leishmania mexicana. Structure. 2000 May 15;8(5):541-52. PMID:10801498

Page seeded by OCA on Tue Feb 17 09:44:44 2009