PDBsum entry: 1gyp

Oxidoreductase (aldehyde(d)-NAD+(a))

PDB id: 1gyp

Contents

Protein chains

358 a.a. *

Ligands

PO4 ×8

NAD ×4

* Residue conservation analysis

PDB id:

1gyp

Name:

Oxidoreductase (aldehyde(d)-NAD+(a))

Title:

Crystal structure of glycosomal glyceraldehyde-3-phosphate dehydrogenase from leishmania mexicana: implications for structure-based drug design and a new position for the inorganic phosphate binding site

Structure:

Glyceraldehyde-3-phosphate dehydrogenase. Chain: a, b, c, d. Synonym: gapdh. Engineered: yes

Source:

Leishmania mexicana. Organism_taxid: 5665. Gene: glyceraldehyde-3-phosphate. Expressed in: escherichia coli. Expression_system_taxid: 562. Dehydrogenase

Biol. unit:

Tetramer (from PQS)

Resolution:

2.80Å R-factor: 0.198

Authors:

H.Kim,I.K.Feil,C.L.M.J.Verlinde,P.H.Petra,W.G.J.Hol

Key ref:

H.Kim et al. (1995). Crystal structure of glycosomal glyceraldehyde-3-phosphate dehydrogenase from Leishmania mexicana: implications for structure-based drug design and a new position for the inorganic phosphate binding site. Biochemistry, 34, 14975-14986. PubMed id: 7578111 DOI: 10.1021/bi00046a004

Date:

01-Aug-95 Release date: 07-Dec-95

Protein chains

Q27890  (G3PG_LEIME) -  Glyceraldehyde-3-phosphate dehydrogenase, glycosomal

Seq: 361 a.a.

Struc: 358 a.a.

Enzyme reactions

• Enzyme class: E.C.1.2.1.12 - Glyceraldehyde-3-phosphate dehydrogenase (phosphorylating).
• Pathway: Glyceraldehyde-3-phosphate Dehydrogenase (phosphorylating)
• Reaction: D-glyceraldehyde 3-phosphate + phosphate + NAD⁺ = 3-phospho-D-glyceroyl phosphate + NADH

D-glyceraldehyde 3-phosphate + phosphate (Bound ligand (Het Group name = PO4) corresponds exactly) + NAD(+) (Bound ligand (Het Group name = NAD) corresponds exactly) = 3-phospho-D-glyceroyl phosphate + NADH

Molecule diagrams generated from .mol files obtained from the KEGG ftp site

 Gene Ontology (GO) functional annotation 

• Cellular component: glycosome (2 terms)
• Biological process: oxidation-reduction process (3 terms)
• Biochemical function: nucleotide binding (6 terms)

reference

DOI no: 10.1021/bi00046a004

Biochemistry 34:14975-14986 (1995)

PubMed id: 7578111

Crystal structure of glycosomal glyceraldehyde-3-phosphate dehydrogenase from Leishmania mexicana: implications for structure-based drug design and a new position for the inorganic phosphate binding site.

H.Kim, I.K.Feil, C.L.Verlinde, P.H.Petra, W.G.Hol.

ABSTRACT

The structure of glycosomal glyceraldehyde-3-phosphate dehydrogenase (GAPDH) from the trypanosomatid parasite Leishmania mexicana has been determined by X-ray crystallography. The protein crystallizes in space group P2(1)2(1)2(1) with unit cell parameters a = 99.0 A, b = 126.5 A, and c = 138.9 A. There is one 156,000 Da protein tetramer per asymmetric unit. The model of the protein with bound NAD+s and phosphates has been refined against 86% complete data from 10.0 to 2.8 A to a crystallographic Rfactor of 0.198. Density modification by noncrystallographic symmetry averaging was used during model building. The final model of the L. mexicana GAPDH tetramer shows small deviations of less than 0.5 degrees from ideal 222 molecular symmetry. The structure of L. mexicana GAPDH is very similar to that of glycosomal GAPDH from the related trypanosomatid Trypanosoma brucei. A significant structural difference between L. mexicana GAPDH and most previously determined GAPDH structures occurs in a loop region located at the active site. This unusual loop conformation in L. mexicana GAPDH occludes the inorganic phosphate binding site which has been seen in previous GAPDH structures. A new inorganic phosphate position is observed in the L. mexicana GAPDH structure. Model building studies indicate that this new anion binding site is well situated for nucleophilic attack of the inorganic phosphate on the thioester intermediate in the GAPDH-catalyzed reaction. Since crystals of L. mexicana GAPDH can be grown reproducibly and diffract much better than those of T. brucei GAPDH, L. mexicana GAPDH will be used as a basis for structure-based drug design targeted against trypanosomatid GAPDHs.