PDBsum entry 3b9m

Lipid binding protein

PDB id

3b9m

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Contents

			Protein chain

					582 a.a. *

			Ligands

					MYR ×6


					AZZ


					SAL ×2

* Residue conservation analysis

PDB id:

3b9m

Links

Name:

Lipid binding protein

Title:

Human serum albumin complexed with myristate, 3'-azido-3'- deoxythymidine (azt) and salicylic acid

Structure:

Serum albumin. Chain: a

Source:

Homo sapiens. Human

Resolution:

2.70Å

R-factor:

0.242

R-free:

0.316

Authors:

L.Zhu,F.Yang,L.Chen,E.J.Meehan,M.Huang

Key ref:

L.Zhu et al. (2008). A new drug binding subsite on human serum albumin and drug-drug interaction studied by X-ray crystallography. J Struct Biol, 162, 40-49. PubMed id: 18258455

Date:

05-Nov-07

Release date:

27-May-08

PROCHECK

	Headers

	References

Protein chain

P02768 (ALBU_HUMAN) - Albumin from Homo sapiens

Seq: Struc:

Seq: Struc:					609 a.a. 582 a.a.

Key:

PfamA domain

Secondary structure

CATH domain

	J Struct Biol 162:40-49 (2008)
PubMed id: 18258455

A new drug binding subsite on human serum albumin and drug-drug interaction studied by X-ray crystallography.
L.Zhu, F.Yang, L.Chen, E.J.Meehan, M.Huang.

ABSTRACT

3'-Azido-3'-deoxythymidine (AZT) is the first clinically effective drug for the treatment of human immunodeficiency virus infection. The drug interaction with human serum albumin (HSA) has been an important component in understanding its mechanism of action, especially in drug distribution and in drug-drug interaction on HSA in the case of multi-drug therapy. We present here crystal structures of a ternary HSA-Myr-AZT complex and a quaternary HSA-Myr-AZT-SAL complex (Myr, myristate; SAL, salicylic acid). From this study, a new drug binding subsite on HSA Sudlow site 1 was identified. The presence of fatty acid is needed for the creation of this subsite due to fatty acid induced conformational changes of HSA. Thus, the Sudlow site 1 of HSA can be divided into three non-overlapped subsites: a SAL subsite, an indomethacin subsite and an AZT subsite. Binding of a drug to HSA often influences simultaneous binding of other drugs. From the HSA-Myr-AZT-SAL complex structure, we observed the coexistence of two drugs (AZT and SAL) in Sudlow site 1 and the competition between these two drugs in subdomain IB. These results provide new structural information on HSA-drug interaction and drug-drug interaction on HSA.

Literature references that cite this PDB file's key reference

PubMed id

Reference

20940056

A.J.Ryan, J.Ghuman, P.A.Zunszain, C.W.Chung, and S.Curry (2011).
Structural basis of binding of fluorescent, site-specific dansylated amino acids to human serum albumin.

J Struct Biol, 174, 84-91.

PDB codes:

2xsi 2xvq 2xvu 2xvv 2xvw 2xw0 2xw1

20737064

F.Zsila, and I.Fitos (2010).
Combination of chiroptical, absorption and fluorescence spectroscopic methods reveals multiple, hydrophobicity-driven human serum albumin binding of the antimalarial atovaquone and related hydroxynaphthoquinone compounds.

Org Biomol Chem, 8, 4905-4914.

19642656

F.Yan, F.Y.Che, D.Rykunov, E.Nieves, A.Fiser, L.M.Weiss, and R.Hogue Angeletti (2009).
Nonprotein based enrichment method to analyze peptide cross-linking in protein complexes.

Anal Chem, 81, 7149-7159.

19601929

S.Guo, X.Shi, F.Yang, L.Chen, E.J.Meehan, C.Bian, and M.Huang (2009).
Structural basis of transport of lysophospholipids by human serum albumin.

Biochem J, 423, 23-30.

PDB code:

3cx9

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.