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PDBsum entry 1i10

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protein ligands Protein-protein interface(s) links
Oxidoreductase PDB id
1i10
Jmol
Contents
Protein chain
(+ 2 more) 331 a.a. *
Ligands
ACT ×8
NAI ×8
OXM ×8
Waters ×652
* Residue conservation analysis
PDB id:
1i10
Name: Oxidoreductase
Title: Human muscle l-lactate dehydrogenase m chain, ternary complex with nadh and oxamate
Structure: L-lactate dehydrogenase m chain. Chain: a, b, c, d, e, f, g, h. Synonym: ldh-a. Engineered: yes
Source: Homo sapiens. Human. Organism_taxid: 9606. Organ: heart. Gene: ldha. Expressed in: escherichia coli bl21. Expression_system_taxid: 511693.
Biol. unit: Tetramer (from PQS)
Resolution:
2.30Å     R-factor:   0.200     R-free:   0.257
Authors: J.A.Read,V.J.Winter,C.M.Eszes,R.B.Sessions,R.L.Brady
Key ref: J.A.Read et al. (2001). Structural basis for altered activity of M- and H-isozyme forms of human lactate dehydrogenase. Proteins, 43, 175-185. PubMed id: 11276087
Date:
30-Jan-01     Release date:   28-Mar-01    
PROCHECK
Go to PROCHECK summary
 Headers
 References

Protein chains
Pfam   ArchSchema ?
P00338  (LDHA_HUMAN) -  L-lactate dehydrogenase A chain
Seq:
Struc:
332 a.a.
331 a.a.
Key:    PfamA domain  Secondary structure  CATH domain

 Enzyme reactions 
   Enzyme class: E.C.1.1.1.27  - L-lactate dehydrogenase.
[IntEnz]   [ExPASy]   [KEGG]   [BRENDA]
      Reaction: (S)-lactate + NAD+ = pyruvate + NADH
(S)-lactate
Bound ligand (Het Group name = OXM)
matches with 71.00% similarity
+
NAD(+)
Bound ligand (Het Group name = NAI)
corresponds exactly
= pyruvate
+ NADH
Molecule diagrams generated from .mol files obtained from the KEGG ftp site
 Gene Ontology (GO) functional annotation 
  GO annot!
  Cellular component     flagellar fibrous sheath   7 terms 
  Biological process     small molecule metabolic process   8 terms 
  Biochemical function     catalytic activity     5 terms  

 

 
    reference    
 
 
Proteins 43:175-185 (2001)
PubMed id: 11276087  
 
 
Structural basis for altered activity of M- and H-isozyme forms of human lactate dehydrogenase.
J.A.Read, V.J.Winter, C.M.Eszes, R.B.Sessions, R.L.Brady.
 
  ABSTRACT  
 
Lactate dehydrogenase (LDH) interconverts pyruvate and lactate with concomitant interconversion of NADH and NAD(+). Although crystal structures of a variety of LDH have previously been described, a notable absence has been any of the three known human forms of this glycolytic enzyme. We have now determined the crystal structures of two isoforms of human LDH-the M form, predominantly found in muscle; and the H form, found mainly in cardiac muscle. Both structures have been crystallized as ternary complexes in the presence of the NADH cofactor and oxamate, a substrate-like inhibitor. Although each of these isoforms has different kinetic properties, the domain structure, subunit association, and active-site regions are indistinguishable between the two structures. The pK(a) that governs the K(M) for pyruvate for the two isozymes is found to differ by about 0.94 pH units, consistent with variation in pK(a) of the active-site histidine. The close similarity of these crystal structures suggests the distinctive activity of these enzyme isoforms is likely to result directly from variation of charged surface residues peripheral to the active site, a hypothesis supported by electrostatic calculations based on each structure. Proteins 2001;43:175-185.
 

Literature references that cite this PDB file's key reference

  PubMed id Reference
20676418 A.D.Moorhouse, C.Spiteri, P.Sharma, M.Zloh, and J.E.Moses (2011).
Targeting glycolysis: a fragment based approach towards bifunctional inhibitors of hLDH-5.
  Chem Commun (Camb), 47, 230-232.  
19575810 A.Chaikuad, and R.L.Brady (2009).
Conservation of structure and activity in Plasmodium purine nucleoside phosphorylases.
  BMC Struct Biol, 9, 42.
PDB codes: 3emv 3enz
18446214 A.A.Brindley, R.W.Pickersgill, J.C.Partridge, D.J.Dunstan, D.M.Hunt, and M.J.Warren (2008).
Enzyme sequence and its relationship to hyperbaric stability of artificial and natural fish lactate dehydrogenases.
  PLoS ONE, 3, e2042.  
  19043979 A.Tylicki, J.Czerniecki, A.Godlewska, M.Kieliszek, T.Zebrowski, T.Bielawski, and B.Wojcik (2008).
Changes in ECG and enzyme activity in rat heart after myocardial infarction: effect of TPP and MnCl2.
  J Physiol Biochem, 64, 93.  
18253497 J.Lemire, R.J.Mailloux, and V.D.Appanna (2008).
Mitochondrial Lactate Dehydrogenase Is Involved in Oxidative-Energy Metabolism in Human Astrocytoma Cells (CCF-STTG1).
  PLoS ONE, 3, e1550.  
17256769 D.O.Cicero, G.M.Contessa, T.A.Pertinhez, M.Gallo, A.M.Katsuyama, M.Paci, C.S.Farah, and A.Spisni (2007).
Solution structure of ApaG from Xanthomonas axonopodis pv. citri reveals a fibronectin-3 fold.
  Proteins, 67, 490-500.
PDB code: 2f1e
17944947 P.Gaspar, A.R.Neves, C.A.Shearman, M.J.Gasson, A.M.Baptista, D.L.Turner, C.M.Soares, and H.Santos (2007).
The lactate dehydrogenases encoded by the ldh and ldhB genes in Lactococcus lactis exhibit distinct regulation and catalytic properties - comparative modeling to probe the molecular basis.
  FEBS J, 274, 5924-5936.  
17640885 S.L.Quaytman, and S.D.Schwartz (2007).
Reaction coordinate of an enzymatic reaction revealed by transition path sampling.
  Proc Natl Acad Sci U S A, 104, 12253-12258.  
16444750 Z.M.Svedruzić, and H.O.Spivey (2006).
Interaction between mammalian glyceraldehyde-3-phosphate dehydrogenase and L-lactate dehydrogenase from heart and muscle.
  Proteins, 63, 501-511.  
16180137 C.T.Culiat, M.L.Klebig, Z.Liu, H.Monroe, B.Stanford, J.Desai, S.Tandan, L.Hughes, M.K.Kerley, D.A.Carpenter, D.K.Johnson, E.M.Rinchik, and Q.Li (2005).
Identification of mutations from phenotype-driven ENU mutagenesis in mouse chromosome 7.
  Mamm Genome, 16, 555-566.  
16848225 P.L.Gorelikov, and S.V.Savelev (2005).
Isoenzyme profile of lactate dehydrogenase in the cranial cervical sympathetic ganglion under normal conditions and during synaptic blockade.
  Bull Exp Biol Med, 140, 690-692.  
15117937 A.Cameron, J.Read, R.Tranter, V.J.Winter, R.B.Sessions, R.L.Brady, L.Vivas, A.Easton, H.Kendrick, S.L.Croft, D.Barros, J.L.Lavandera, J.J.Martin, F.Risco, S.García-Ochoa, F.J.Gamo, L.Sanz, L.Leon, J.R.Ruiz, R.Gabarró, A.Mallo, and F.Gómez de las Heras (2004).
Identification and activity of a series of azole-based compounds with lactate dehydrogenase-directed anti-malarial activity.
  J Biol Chem, 279, 31429-31439.
PDB codes: 1t24 1t25 1t26 1t2c 1t2d 1t2e 1t2f
12555229 R.A.Philibert, J.J.Nelson, H.K.Sandhu, R.R.Crowe, and W.H.Coryell (2003).
Association of an exonic LDHA polymorphism with altered respiratory response in probands at high risk for panic disorder.
  Am J Med Genet B Neuropsychiatr Genet, 117, 11-17.  
12145195 R.M.Crawford, G.R.Budas, S.Jovanović, H.J.Ranki, T.J.Wilson, A.M.Davies, and A.Jovanović (2002).
M-LDH serves as a sarcolemmal K(ATP) channel subunit essential for cell protection against ischemia.
  EMBO J, 21, 3936-3948.  
The most recent references are shown first. Citation data come partly from CiteXplore and partly from an automated harvesting procedure. Note that this is likely to be only a partial list as not all journals are covered by either method. However, we are continually building up the citation data so more and more references will be included with time. Where a reference describes a PDB structure, the PDB codes are shown on the right.