Jasper Small Lactate Sandbox 1

spinqualitylabelsall models PDB ID 1i10 Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image
1i10, resolution 2.30Å ()
Ligands:	, ,
Gene:	LDHA (Homo sapiens)
Activity:	L-lactate dehydrogenase, with EC number 1.1.1.27
Related:	1i0z, 9ldt, 5ldh, 1ldg
Structural annotation: Resources: CATH : 1I10A02, 1I10A01, 1I10B01, 1I10B02, 1I10C02, 1I10C01, 1I10D01, 1I10D02, 1I10E02, 1I10E01, 1I10F01, 1I10F02, 1I10G02, 1I10G01, 1I10H01, 1I10H02 InterPro : Ipr001557, Ipr001236, Ipr011304 Pfam : PF00056, PF02866 SCOP : d1i10a1, d1i10a2, d1i10b2, d1i10b1, d1i10c2, d1i10c1, d1i10d1, d1i10d2, d1i10e1, d1i10e2, d1i10f1, d1i10f2, d1i10g2, d1i10g1, d1i10h2, d1i10h1 UniProt : P00338
Functional annotation: Cellular component: cytosol cytoplasm Biological process: anaerobic glycolysis cellular carbohydrate metabolic process glycolysis tricarboxylic acid cycle intermediate metabolic process Molecular function: L-lactate dehydrogenase activity oxidoreductase activity, acting on the CH-OH group of donors, NAD or NADP as acceptor oxidoreductase activity protein binding
Evolutionary conservation: Toggle Conservation Colors: Rows = identical sequences: Further Information: Caveats, Explanation, Complete Results at ConSurfDB
Resources:	FirstGlance, OCA, RCSB, PDBsum
Coordinates:	save as pdb, mmCIF, xml

Lactate DehydrogenaseLactate Dehydrogenase

Lactate Dehydrogenase (LDH) is an important enzyme in humans. It occurs in different regions of the body, each region having a unique conformation of different subunits. The Jmole image shown is that of LDH-5, the form found in skeleton muscle and the liver.

FunctionFunction

Catalytic function of LDH (1)

LDH preforms an important metabolic function in the body. The enzyme catalyzes both the conversion of pyruvate to lactose as well as the conversion of lactose to pyruvate. The conversion of pyruvate to lactose occurs in the muscles of the body when oxygen is absent. The lactate acid is then moved back to the liver where LDH catalyzes the Cori cycle which converts the lactose back into pyruvate. The reaction is also important as it is coupled with the interconversion of NADH and NAD+.

FormsForms

LDH is a quaternary protein formed of the combination of two subunits, M and H (Muscle and Heart) into a structure of four of the subunits. The various combinations found in the human body are:

• (4H) Heart
• (3H1M) Reticuloendothelial
• (2H2M) Lungs
• (1H3M) Kidneys
• (4M) Muscle and Liver

CatalysisCatalysis

Studies have shown that the reaction mechanism of LDH follows an ordered sequence. In order for lactate to be oxidized NAD+ must bind to the enzyme first followed by lactate. Transfer of a hydride ion then happens quickly in either direction giving a mixture of the two teranary complexes, enzyme-NAD+-lactate and enzyme-NADH-pyruvate. Finally pyruvate dissociates from the enzyme followed by NADH. The rate limiting step in this reaction is the rate of dissociation of NADH. The same holds true in the reverse reaction that the coenzyme, NADH, must bind first before the substrate, pyruvate, can bind. The conversion of pyruvate to lactate with the subsequent regeneration of NAD+ is a very favorable(1).

(1)

Important Sites:

StructureStructure

The secondary structure of LDH is comprised of 40% alpha helices and 23% beta sheets.(2)

SCOP 1I10- a/b Mainly parallel beta sheets (beta-alpha-beta units) 1I0Z- a/b Mainly parallel beta sheets (beta-alpha-beta units)

ReferenceReference

1- http://www.bioc.aecom.yu.edu/labs/calllab/highlights/LDH.htm 2- http://www.cheric.org/ippage/e/ipdata/2004/05/file/e200405-701.pdf