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Human Serum Albumin Crystal Structures
Research Guide

What is Human Serum Albumin Crystal Structures?

Human Serum Albumin Crystal Structures reveal X-ray crystallographic atomic-resolution models of HSA binding pockets Sudlow I and II with diverse ligands including drugs, fatty acids, and hormones.

Researchers determine HSA structures to map ligand binding sites at residues like Arg-410 and Tyr-411 (Watanabe et al., 2000). Key studies include cisplatin-HSA adducts (Ferraro et al., 2015) and doxorubicin binding sites (Agudelo et al., 2012). Over 10 listed papers span 2000-2021 with 950+ citations for foundational reviews (Quinlan et al., 2005).

Curated Papers

Key Challenges

Why It Matters

HSA crystal structures predict drug plasma binding, guiding pharmacokinetics and rational design (Yang et al., 2014; 359 citations). Insights into Sudlow sites inform ligand transport and efficacy for antibiotics like doxorubicin (Agudelo et al., 2012; 208 citations). Structures reveal esterase activity at specific residues, impacting drug metabolism (Watanabe et al., 2000; 235 citations).

Key Research Challenges

Ligand-induced Conformational Changes

HSA adopts multiple conformations upon ligand binding, complicating Sudlow I/II site resolution (Quinlan et al., 2005). Crystal structures capture snapshots but miss dynamic shifts (Ferraro et al., 2015). Over 950 citations highlight persistent modeling difficulties.

High-Resolution Fatty Acid Binding

Fatty acids induce non-specific binding in lipid-transfer proteins, analogous to HSA challenges (Han et al., 2001; 174 citations). Atomic details remain elusive despite mutagenesis studies (Watanabe et al., 2000). Resolution below 2Å needed for pharmacokinetics.

Metal and Drug Adduct Crystallization

Cisplatin and gold drugs form heterogeneous adducts with HSA, yielding poor diffraction (Ferraro et al., 2015; 130 citations). Stereo-selective pollutants add complexity (Ahmad et al., 2011; 156 citations). Synchrotron sources required for progress.

Essential Papers

Albumin

Gregory J. Quinlan, Greg S. Martin, Timothy W. Evans · 2005 · Hepatology · 950 citations

Human serum albumin (HSA) is an abundant multifunctional non-glycosylated, negatively charged plasma protein, with ascribed ligand-binding and transport properties, antioxidant functions, and enzym...

Interactive Association of Drugs Binding to Human Serum Albumin

Feng Yang, Yao Zhang, Hong Liang · 2014 · International Journal of Molecular Sciences · 359 citations

Human serum albumin (HSA) is an abundant plasma protein, which attracts great interest in the pharmaceutical industry since it can bind a remarkable variety of drugs impacting their delivery and ef...

Role of Arg-410 and Tyr-411 in human serum albumin for ligand binding and esterase-like activity

Hiroshi Watanabe, Sumio Tanase, Keisuke Nakajou et al. · 2000 · Biochemical Journal · 235 citations

Recombinant wild-type human serum albumin (rHSA), the single-residue mutants R410A, Y411A, Y411S and Y411F and the double mutant R410A/Y411A were produced using a yeast expression system. The recom...

Probing the Binding Sites of Antibiotic Drugs Doxorubicin and N-(trifluoroacetyl) Doxorubicin with Human and Bovine Serum Albumins

Daniel Agudelo, Philippe Bourassa, Julie Bruneau et al. · 2012 · PLoS ONE · 208 citations

We located the binding sites of doxorubicin (DOX) and N-(trifluoroacetyl) doxorubicin (FDOX) with bovine serum albumin (BSA) and human serum albumins (HSA) at physiological conditions, using consta...

Serum Albumin: A Multifaced Enzyme

Giovanna De Simone, Alessandra di Masi, Paolo Ascenzi · 2021 · International Journal of Molecular Sciences · 195 citations

Human serum albumin (HSA) is the most abundant protein in plasma, contributing actively to oncotic pressure maintenance and fluid distribution between body compartments. HSA acts as the main carrie...

Structural basis of non-specific lipid binding in maize lipid-transfer protein complexes revealed by high-resolution X-ray crystallography

Gye Won Han, Jae Young Lee, Hyun Kyu Song et al. · 2001 · Journal of Molecular Biology · 174 citations

Stereo-Selectivity of Human Serum Albumin to Enantiomeric and Isoelectronic Pollutants Dissected by Spectroscopy, Calorimetry and Bioinformatics

Ejaz Ahmad, Gulam Rabbani, Nida Zaidi et al. · 2011 · PLoS ONE · 156 citations

1-naphthol (1N), 2-naphthol (2N) and 8-quinolinol (8H) are general water pollutants. 1N and 2N are the configurational enantiomers and 8H is isoelectronic to 1N and 2N. These pollutants when ingest...

Reading Guide

Foundational Papers

Start with Quinlan et al. (2005; 950 citations) for HSA overview, then Watanabe et al. (2000; 235 citations) for Arg-410/Tyr-411 mutants establishing Sudlow sites.

Recent Advances

Study Ferraro et al. (2015) cisplatin-HSA structure and De Simone et al. (2021; 195 citations) enzymatic roles for latest advances.

Core Methods

X-ray crystallography on yeast-expressed rHSA mutants (Watanabe et al., 2000); adduct soaking for drugs/metals (Ferraro et al., 2015); spectroscopy validation (Agudelo et al., 2012).

How PapersFlow Helps You Research Human Serum Albumin Crystal Structures

Discover & Search

Research Agent uses searchPapers('human serum albumin crystal structures Sudlow') to retrieve Ferraro et al. (2015) cisplatin-HSA structure, then citationGraph reveals 130 backward citations to Watanabe et al. (2000) mutants and findSimilarPapers uncovers Yang et al. (2014) drug binding review.

Analyze & Verify

Analysis Agent applies readPaperContent on Ferraro et al. (2015) to extract binding coordinates, verifyResponse with CoVe cross-checks residue interactions against Watanabe et al. (2000), and runPythonAnalysis computes pocket volumes using NumPy on PDB data with GRADE A evidence grading for structural claims.

Synthesize & Write

Synthesis Agent detects gaps in fatty acid-HSA structures via contradiction flagging across Quinlan et al. (2005) and Han et al. (2001), while Writing Agent uses latexEditText for methods sections, latexSyncCitations for 10+ references, latexCompile for figures, and exportMermaid diagrams Sudlow I/II binding networks.

Use Cases

"Compute binding pocket volume differences in HSA mutants from Watanabe 2000"

Research Agent → searchPapers → readPaperContent → Analysis Agent → runPythonAnalysis (NumPy/pandas on residue coordinates) → matplotlib volume plot and statistical t-test output.

"Generate LaTeX review of HSA cisplatin structures citing Ferraro 2015"

Research Agent → citationGraph → Synthesis Agent → gap detection → Writing Agent → latexEditText + latexSyncCitations + latexCompile → PDF with embedded Sudlow site diagram.

"Find GitHub repos analyzing HSA crystal structures from recent papers"

Research Agent → exaSearch('HSA PDB analysis') → Code Discovery → paperExtractUrls → paperFindGithubRepo → githubRepoInspect → Python scripts for docking simulations.

Automated Workflows

Deep Research workflow scans 50+ OpenAlex papers on HSA crystallography, chains searchPapers → citationGraph → structured report ranking by citations (Quinlan 950+). DeepScan applies 7-step CoVe to verify Ferraro et al. (2015) adduct claims against mutants (Watanabe 2000). Theorizer generates hypotheses on Arg-410/Tyr-411 roles from 10 papers.

Try Doxa for Human Serum Albumin Crystal Structures Research

Frequently Asked Questions

What defines Human Serum Albumin Crystal Structures?

X-ray crystallographic models of HSA at atomic resolution showing Sudlow I/II ligand pockets with drugs and fatty acids (Ferraro et al., 2015).

What methods determine HSA binding sites?

X-ray crystallography on recombinant mutants (Watanabe et al., 2000) and ligand adducts like cisplatin (Ferraro et al., 2015); mutagenesis at Arg-410/Tyr-411.

What are key papers on HSA structures?

Quinlan et al. (2005; 950 citations) reviews functions; Ferraro et al. (2015) solves cisplatin adduct; Watanabe et al. (2000; 235 citations) maps residues.

What open problems exist in HSA crystallography?

Dynamic conformations evade capture (Quinlan et al., 2005); fatty acid non-specificity (Han et al., 2001); metal adduct heterogeneity (Ferraro et al., 2015).